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MaR1治疗脂多糖诱导的急性肺损伤小鼠的效果和机制 被引量:2
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作者 王强 林飞 +3 位作者 胡召锟 林锦源 黄冰 潘灵辉 《广东医学》 CAS 2021年第8期909-913,共5页
目的探讨Maresin-1(MaR1)治疗脂多糖(LPS)诱导的急性肺损伤(ALI)小鼠的效果和机制。方法将雄性SPF级BALB/c小鼠45只随机分为3组。对照组经口气管插管滴入3 mg/kg生理盐水。LPS组经口气管插管滴入3 mg/kg LPS。MaR1组经口气管插管滴入3 m... 目的探讨Maresin-1(MaR1)治疗脂多糖(LPS)诱导的急性肺损伤(ALI)小鼠的效果和机制。方法将雄性SPF级BALB/c小鼠45只随机分为3组。对照组经口气管插管滴入3 mg/kg生理盐水。LPS组经口气管插管滴入3 mg/kg LPS。MaR1组经口气管插管滴入3 mg/kg LPS,1 h后尾静脉注射1 ng/只MaR1。对比分析3组小鼠肺组织损伤评分、免疫印迹分析小鼠肺组织MAPKs、核因子-κB(NF-κB)蛋白表达,以及氧化应激标记分析3组小鼠肺组织核因子-E2相关因子2(Nrf-2)表达和抗氧化酶的情况。结果与LPS组比较,MaR1组能改善LPS诱导的ALI小鼠肺组织损伤评分(P=0.000);MaR1组能显著抑制LPS诱导的ALI小鼠MAPKs和p65NF-κB的磷酸化,两组间差异均有统计学意义(P<0.05);MaR1组通过上调抗氧化酶增加Nrf-2的核转运,两组间差异均有统计学意义(P<0.05);MaR1组抑制了LPS诱导的ALI模型肺组织中活性氧介导的氧化应激反应,两组间差异均有统计学意义(P<0.05)。结论MaR1治疗小鼠ALI机制可能是通过抑制MAPK和NF-κB的磷酸化,同时活化多种抗氧化酶保护肺组织有关。 展开更多
关键词 脂多糖 急性肺损伤 mar1 核因子-E2相关因子2
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MaR1治疗脂多糖诱导的小鼠急性肺损伤的应用价值研究 被引量:1
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作者 王强 林飞 +3 位作者 胡召锟 林锦源 黄冰 潘灵辉 《广西医科大学学报》 CAS 2020年第5期832-836,共5页
目的:研究MaR1治疗脂多糖(LPS)诱导的小鼠急性肺损伤(ALI)的应用价值。方法:雄性SPF级BALB/c小鼠45只,平均随机分为对照组、LPS组、MaR1组,记录、比较3组之间支气管肺泡灌洗液(BALF)细胞计数、细胞因子和蛋白质含量、肺组织损伤评分及... 目的:研究MaR1治疗脂多糖(LPS)诱导的小鼠急性肺损伤(ALI)的应用价值。方法:雄性SPF级BALB/c小鼠45只,平均随机分为对照组、LPS组、MaR1组,记录、比较3组之间支气管肺泡灌洗液(BALF)细胞计数、细胞因子和蛋白质含量、肺组织损伤评分及其免疫印迹情况。结果:与LPS组比较,MaR1组BALF中的炎症细胞数量减少伴细胞质量减轻(P<0.05);肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)、白介素-6(IL-6)表达水平下降(P<0.05);肺组织损伤评分显著降低(P<0.05);MaR1组核因子核因子E-2相关因子2(Nrf2)、血红素氧合酶-1(HO-1)和醌NADH脱氢酶1(NQO1)表达水平明显增加(P<0.05)。结论:MaR1能有效抑制LPS诱导的ALI小鼠模型的炎性反应,并介导多种抗氧化酶保护肺组织免于损伤,其作用机制可能与Nrf2的激活密切相关。 展开更多
关键词 脂多糖 急性肺损伤 mar1 支气管肺泡灌洗液 氧化应激
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Proton pitch angle distributions in the Martian induced magnetosphere: A survey of Tianwen-1 Mars Ion and Neutral Particle Analyzer observations 被引量:1
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作者 TaiFeng Jin BinBin Ni +14 位作者 LingGao Kong AiBing Zhang Lei Li Song Fu Xing Cao WenYa Li BinBin Tang LiangHai Xie YiTeng Zhang ShuYue Pang XiaoTong Yun HengLe Du FuHao Qiao LiMin Wang JiJie Ma 《Earth and Planetary Physics》 CAS CSCD 2023年第5期533-539,共7页
The pitch angle distributions of ions and electrons can be affected by various processes;thus,they can serve as an important indicator of the physical mechanisms driving the dynamics of space plasmas.From observations... The pitch angle distributions of ions and electrons can be affected by various processes;thus,they can serve as an important indicator of the physical mechanisms driving the dynamics of space plasmas.From observations from the Mars Ion and Neutral Particle Analyzer onboard the Tianwen-1 orbiter,we calculated the pitch angle distributions of protons in the Martian induced magnetosphere by using information from the magnetohydrodynamically simulated magnetic field,and we statistically analyzed the spatial occurrence pattern of different types of pitch angle distributions.Even though no symmetrical features were seen in the dataset,we found the dominance of the field-aligned distribution type over the energy range from 188 to 6232 eV.Maps of the occurrence rate showed the preferential presence of a trapped-like distribution at the lower altitudes of the surveyed nightside region.Although our results are more or less restricted by the adopted magnetic field,they indicate the complexity of the near-Mars proton pitch angle distributions and infer the possibility of wave–particle interactions in the Martian induced magnetosphere. 展开更多
关键词 Martian plasma environment ion pitch angle distribution Tianwen-1 Mars Ion and Neutral Particle Analyzer(MINPA)
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MARS1基因变异所致间质性肺病及肝病1例
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作者 彭文静 朱燕 +3 位作者 王来栓 陆炜 杨琳 朱丽 《中国当代儿科杂志》 CAS CSCD 北大核心 2023年第11期1186-1190,共5页
患儿,女,4个月9 d,因反复发热、咳嗽伴肝大1月余入院。患儿系健康足月儿,出生史正常,自生后2个月22 d出现反复发热、咳嗽,不能离氧,胸部影像学提示双肺弥漫性病变,纤维支气管镜检查示双肺间质样改变,考虑存在间质性肺病。患儿同时存在... 患儿,女,4个月9 d,因反复发热、咳嗽伴肝大1月余入院。患儿系健康足月儿,出生史正常,自生后2个月22 d出现反复发热、咳嗽,不能离氧,胸部影像学提示双肺弥漫性病变,纤维支气管镜检查示双肺间质样改变,考虑存在间质性肺病。患儿同时存在肝大、贫血、高脂血症、甲状腺功能减退、营养不良等。基因检测提示患儿存在MARS1基因复合杂合变异。该变异可致间质性肺病及肝病,是一种在婴儿期或幼儿期发病的严重罕见疾病,为常染色体隐性遗传,以婴儿或幼儿早期呼吸功能不全和肝病为特征。自2013年该病被首次报道以来,至2023年6月全球仅有38例相关病例报道。该文报道1例MARS1基因变异所致间质性肺病及肝病患儿的多学科诊疗。 展开更多
关键词 间质性肺病及肝病 MARS1基因 多系统疾病 甲硫氨酸 婴儿
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Reversal of Adriamycin Resistance of Hepatocellular Carcinoma by Targeting with Recombined Adenovirus Caning Antisense mdr1 RNA 被引量:1
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作者 Xiong Ding Ying Mei Yujun Shi Jianping Gong Xuhong Li Yong Peng Yong Liu Chang'an Liu 《Chinese Journal of Clinical Oncology》 CSCD 2006年第1期32-36,共5页
OBJECTIVE Chemotherapy is an important therapy for hepatocellular carcinoma (HCC). However, it is not effective in many cases due to recurrence and metastasis even if the initial treatment produces a response. Multi... OBJECTIVE Chemotherapy is an important therapy for hepatocellular carcinoma (HCC). However, it is not effective in many cases due to recurrence and metastasis even if the initial treatment produces a response. Multidrug resistance (MDR) is considered to be one of the considerable causes. The aim of this study was to reverse MDR of HepG2/ADM cells by blocking mdr1 with an adenovirus vector carrying antisense mdr1 in a tumor transplantated in athymic mice. METHODS PCMV IE was removed from the pshuttle vector. A 0.3 kb AFP promoter was inserted into the pshuttle vector and pCMV changed into pAFP. The pAFP and asmdr1 PCR products were doubly digested with Kpnl and Apal, the digested products were ligated by T4 ligase, the asmdr1 gene was inserted into pAFP and a newly plasmid pAFP-asmdr1 was constructed. Following digestion with PI-SceI/I-Ceu I, pAFP-asmdr1 was ligated with Adeno-X genome DNA and amplified in E.coli XL1-Blue. The HEK293 cells were transfected and virus collected. The HepG2 MDR cells (HepG2/ADM) were induced by graded resistance to ADM and were inoculated into athymic mice. After adeno-asmdr1 was injected, the expression of mdr1-mRNA and the volume of the transplantated tumor and its cells were observed. RESULTS Following injection with Adeno-asmdr1, the tumor volume in the ADM+Adeno-asmdr1 group did not increase. However the tumor volume in the PBS plus ADM group did significantly increase (P〈0.05). In the tumor xenograft cells, mdr1 mRNA in the xenografts was assessed by RT-PCR and was found to be reduced at 1 week and 4 weeks in the ADM+asmdr1 group, but it was stable in the ADM group. It was only 20% in the ADM+asmdr1 group compared to the ADM group at the 4th week (P〈0.05). Evidence of apoptosis was observed in the tumor xenograft cells treated with Adeno-asmdr1, but there was rare or no apoptosis in the group treated with ADM and PBS. CONCLUSION Adenovirus carrying antisense mdr1 RNA can partially reverse the MDR of HepG2/ADM cells and inhibit tumor growth by down-regulating mdr1 mRNA resulting in tumor cell apoptosis. 展开更多
关键词 hepatocellular carcinoma multidrug resistance ADENOVIRUS antisense technology mar1.
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Maresin 1激活Nrf2信号通路减轻低氧/复氧诱导的心肌细胞损伤
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作者 杨光 钟妮尔 +2 位作者 王瑞 李炜 安慧仙 《山西医科大学学报》 CAS 2022年第12期1541-1549,共9页
目的探讨Maresin 1(MaR1)对低氧/复氧诱导的心肌细胞损伤的影响和作用机制。方法培养小鼠HL-1心肌细胞,采用低氧孵育6 h和复氧12 h来构建低氧/复氧细胞模型。小鼠HL-1心肌细胞分为常氧对照组(常氧培养18 h)、低氧/复氧组(低氧培养6 h,... 目的探讨Maresin 1(MaR1)对低氧/复氧诱导的心肌细胞损伤的影响和作用机制。方法培养小鼠HL-1心肌细胞,采用低氧孵育6 h和复氧12 h来构建低氧/复氧细胞模型。小鼠HL-1心肌细胞分为常氧对照组(常氧培养18 h)、低氧/复氧组(低氧培养6 h,然后复氧处理12 h)、低氧/复氧+溶剂组(加入溶剂对照二甲基亚砜预处理30 min后,进行低氧/复氧处理)、低氧/复氧+MaR1组(加入50 nmol/L的MaR1预处理30 min后,进行低氧/复氧处理)和低氧/复氧+MaR1+ML385组(加入50 nmol/L的MaR1和5μmol/L的ML385预处理30 min后,进行低氧/复氧处理)。采用细胞计数试剂盒-8(cell counting kit-8,CCK-8)方法检测细胞存活率。乳酸脱氢酶(lactate dehydrogenase,LDH)细胞毒性检测试剂盒检测细胞损伤。TUNEL试剂盒检测细胞凋亡。活性氧(reactive oxygen species,ROS)试剂盒法检测ROS水平。丙二醛(malondialdehyde,MDA)试剂盒法检测MDA含量。超氧化物歧化酶(superoxide dismutase,SOD)试剂盒法检测SOD酶活性。利用Western blotting检测核转录因子E2相关因子2(nuclear factor-erythroid 2-related factor 2,Nrf2)、血红素加氧酶-1(heme oxygenase-1,HO-1)和醌氧化还原酶1(quinone oxidoreductase 1,NQO1)的蛋白表达水平。结果与常氧对照组比较,低氧/复氧组心肌细胞存活率显著降低(P<0.01),凋亡心肌细胞数量显著增加(P<0.01),ROS产生水平显著升高(P<0.01),MDA含量显著增加(P<0.01),SOD酶活性显著降低(P<0.01)。与低氧/复氧组和低氧/复氧+溶剂组比较,低氧/复氧+MaR1组心肌细胞存活率显著上升(P<0.01),凋亡心肌细胞数量显著减少(P<0.01),ROS产生水平显著降低(P<0.01),MDA含量显著减少(P<0.01),SOD酶活性显著升高(P<0.01)。与常氧对照组比较,低氧/复氧组Nrf2蛋白在细胞核中的表达量显著增加(P<0.05),Nrf2下游基因HO-1和NQO-1表达水平显著提高(P<0.01)。与低氧/复氧组和低氧/复氧+溶剂组比较,低氧/复氧+MaR1组Nrf2蛋白在细胞核中的表达量显著增加(P<0.01),HO-1和NQO-1表达水平显著提高(P<0.01)。与低氧/复氧+MaR1组比较,低氧/复氧+MaR1+ML385组Nrf2蛋白在细胞核中的表达量显著减少(P<0.01),凋亡心肌细胞数量显著增加(P<0.01),ROS产生水平显著升高(P<0.01)。结论MaR1通过激活Nrf2信号通路减轻低氧/复氧诱导的心肌细胞损伤。 展开更多
关键词 心肌细胞 低氧/复氧 mar1 NRF2 氧化应激
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Maresin 1抑制核因子κB/胱天蛋白酶-3/焦孔素E信号途径减轻肝脏缺血再灌注损伤 被引量:1
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作者 曾侯帅 王运兵 +1 位作者 陈刘璇子 朱鹏 《中华肝脏病杂志》 CAS CSCD 北大核心 2023年第6期594-600,共7页
目的探讨Maresin 1(MaR1)在肝缺血再灌注损伤(HIRI)中的作用。方法建立HIRI模型,随机分为假手术组(Sham组)、缺血再灌注组(IR组)、MaR1缺血再灌注组(MaR1+IR组)。在麻醉前0.5 h尾静脉注射MaR180 ng/只,打开腹腔夹闭左、中肝叶动脉和门静... 目的探讨Maresin 1(MaR1)在肝缺血再灌注损伤(HIRI)中的作用。方法建立HIRI模型,随机分为假手术组(Sham组)、缺血再灌注组(IR组)、MaR1缺血再灌注组(MaR1+IR组)。在麻醉前0.5 h尾静脉注射MaR180 ng/只,打开腹腔夹闭左、中肝叶动脉和门静脉,缺血1h后恢复供血,再灌注6 h后处死小鼠收集血液、肝组织,Sham组仅打开、关闭腹腔。RAW267.4巨噬细胞在缺氧前0.5 h给予MaR150 ng/ml,行缺氧8 h复氧2 h,分为对照组(Con组)、缺氧复氧组(HR组)、MaR1缺氧复氧组(MaR1+HR组)、Z-DEVD-FMK缺氧复氧组(HR+Z组)、MaR1+Z-DEVD-FMK缺氧复氧组(MaR1+HR+Z组),Con组未做任何处理,收集细胞和上清液。组间比较采用单因素方差分析,其中两两比较采用LSD-t检验。结果与Sham组相比,IR组丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、白细胞介素(IL)-1β、IL-18水平明显升高(P<0.05),病理改变明显;MaR1+IR组水平较前降低(P<0.05)、病理改变减轻。与Con组比较,HR组IL-1β和IL-18水平升高(P<0.05),MaR1+HR组IL-1β和IL-18水平较前降低(P<0.05)。蛋白质印迹法检测胱天蛋白酶(caspase)-3、焦孔素(GSDM)E、GSDME-N蛋白的表达,HR组和IR组明显高于其他组,经MaR1预处理后表达降低。为了探究MaR1在HIRI中的机制,用Z-DEVD-FMK抑制caspase-3的表达。与HR组比较,HR+Z组IL-1β和IL-18水平降低(P<0.05),caspase-3、GSDME、GSDME-N表达减少、核因子κB表达增加,经MaR1预处理后核因子κB表达降低。MaR1+HR组与MaR1+HR+Z组比较,结果差异无统计学意义(P>0.05)。结论MaR1通过抑制核因子κB活化、caspase-3/GSDME介导的炎性反应,减轻HIRI。 展开更多
关键词 缺血再灌注损伤 胱天蛋白酶-3 mar1 细胞焦亡
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The fungal UmSrt1 and maize ZmSUT1 sucrose transporters battle for plant sugar resources 被引量:7
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作者 Anke Wittek Ingo Dreyer +3 位作者 Khaled A.S. Al-Rasheid Norbert Sauer Rainer Hedrich Dietmar Geiger 《Journal of Integrative Plant Biology》 SCIE CAS CSCD 2017年第6期422-435,共14页
The biotrophic fungus Ustilago maydis causes corn smut disease, inducing tumor formation in its host Zea mays. Upon infection, the fungal hyphae invaginate the plasma membrane of infected maize ceils, establishing an ... The biotrophic fungus Ustilago maydis causes corn smut disease, inducing tumor formation in its host Zea mays. Upon infection, the fungal hyphae invaginate the plasma membrane of infected maize ceils, establishing an interface where pathogen and host are separated only by their plasma membranes. At this interface the fungal and maize sucrose transporters, UmSrtl and ZmSUT1, compete for extracellular sucrose in the corn smut/maize pathos- ystem. Here we biophysically characterized ZmSUT1 and UmSrtl in Xenopus oocytes with respect to their voltage-, pH- and substrate-dependence and determined affinities toward protons and sucrose. In contrast to ZmSUT% UmSrtl has a high affinity for sucrose and is relatively pH- and voltage-independent. Using these quantitative parameters, we developed a mathematical model to simulate the competition for extracellular sucrose at the contact zone between the fungus and the host plant. This approach revealed that UmSrtl exploits the apoplastic sucrose resource, which forces the plant transporter into a sucrose export mode providing the fungus with sugar from the phloem. Importantly, the high sucrose concen- tration in the phloem appeared disadvantageous for the ZmSUT1 preventing sucrose recovery from the apoplastic space in the fungus/plant interface. 展开更多
关键词 William J. Lucas University of California Davis USAReceived Mar. 1 2017 Accepted Mar. 10 2017 Online on Mar. 15 2017
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