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Aldo-keto reductase family member C3(AKR1C3)promotes hepatocellular carcinoma cell growth by producing prostaglandin F2α 被引量:1
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作者 KUO-SHYANG JENG PO-YU CHENG +5 位作者 YUEH-HSIEN LIN PO-CHUN LIU PING-HUI TSENG YU-CHAO WANG CHIUNG-FANG CHANG CHUEN-MIIN LEU 《Oncology Research》 SCIE 2024年第1期163-174,共12页
Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chem... Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chemotherapy.Therefore,new therapeutic targets are needed.We analyzed gene expression profiles between HCC tissues and normal adjacent tissues from public databases and found that the expression of genes involved in lipid metabolism was significantly different.The analysis showed that AKR1C3 was upregulated in tumors,and high AKR1C3 expression was associated with a poorer prognosis in HCC patients.In vitro,assays demonstrated that the knockdown of AKR1C3 or the addition of the AKR1C3 inhibitor indomethacin suppressed the growth and colony formation of HCC cell lines.Knockdown of AKR1C3 in Huh7 cells reduced tumor growth in vivo.To explore the mechanism,we performed pathway enrichment analysis,and the results linked the expression of AKR1C3 with prostaglandin F2 alpha(PGF2a)downstream target genes.Suppression of AKR1C3 activity reduced the production of PGF2a,and supplementation with PGF2a restored the growth of indomethacin-treated Huh7 cells.Knockdown of the PGF receptor(PTGFR)and treatment with a PTGFR inhibitor significantly reduced HCC growth.We showed that indomethacin potentiated the sensitivity of Huh7 cells to sorafenib.In summary,our results indicate that AKR1C3 upregulation may promote HCC growth by promoting the production of PGF2α,and suppression of PTGFR limited HCC growth.Therefore,targeting the AKR1C3-PGF2a-PTGFR axis may be a new strategy for the treatment of HCC. 展开更多
关键词 Hepatocellular carcinoma Aldo-keto reductase family member C3 Prostaglandin F2 alpha Prostaglandin F receptor
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Depositional model of the Member Deng-2 marginal microbial mound-bank complex of the Dengying Formation in the southwestern Sichuan Basin, SW China: Implications for the Ediacaran microbial mound construction and hydrocarbon exploration
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作者 Jin-Min Song Xin Jin +10 位作者 Zhong Luo Shu-Gen Liu Shao-Bo Liu Xing-Zhi Ma Zhi-Wu Li Xue-Song Lu Ling-Li Zhao Ke-Ran Li Jia-Xin Ren Li-Zhou Tian Hao-Shuang Deng 《Petroleum Science》 SCIE EI CAS CSCD 2024年第2期806-822,共17页
Recent advances in hydrocarbon exploration have been made in the Member Deng-2 marginal microbial mound-bank complex reservoirs of the Dengying Formation in the western Sichuan Basin, SW China,where the depositional p... Recent advances in hydrocarbon exploration have been made in the Member Deng-2 marginal microbial mound-bank complex reservoirs of the Dengying Formation in the western Sichuan Basin, SW China,where the depositional process is regarded confusing. The microfacies, construction types, and depositional model of the Member Deng-2 marginal microbial mound-bank complex have been investigated using unmanned aerial vehicle photography, outcrop section investigation, thin section identification,and seismic reflections in the southwestern Sichuan Basin. The microbialite lithologic textures in this region include thrombolite, dendrolite, stromatolite, fenestral stromatolite, spongiostromata stone,oncolite, aggregated grainstone, and botryoidal grapestone. Based on the comprehensive analysis of“depositional fabrics-lithology-microfacies”, an association between a fore mound, mound framework,and back mound subfacies has been proposed based on water depth, current direction, energy level and lithologic assemblages. The microfacies of the mound base, mound core, mound flank, mound cap, and mound flat could be recognized among the mound framework subfacies. Two construction types of marginal microbial mound-bank complex have been determined based on deposition location, mound scale, migration direction, and sedimentary facies association. Type Jinkouhe microbial mound constructions(TJMMCs) develop along the windward margin owing to their proximity to the seaward subfacies fore mound, with a northeastwardly migrated microbial mound on top of the mud mound,exhibiting the characteristics of large-sized mounds and small-sized banks in the surrounding area. Type E'bian microbial mound constructions(TEMMCs) primarily occur on the leeward margin, resulting from the presence of onshore back mound subfacies, with the smaller southwestward migrated microbial mounds existing on a thicker microbial flat. The platform margin microbial mound depositional model can be correlated with certain lateral comparison profile and seismic reflection structures in the 2D seismic section, which can provide references for future worldwide exploration. Microbial mounds with larger buildups and thicker vertical reservoirs are typically targeted on the windward margin, while small-sized microbial mounds and flats with better lateral connections are typically focused on the leeward margin. 展开更多
关键词 Sichuan Basin The member Deng-2 Marginal microbial mound-bank complex Depositional model Exploration implications
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MiRNA-145-5p inhibits gastric cancer progression via the serpin family E member 1-extracellular signal-regulated kinase-1/2 axis
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作者 Hong-Xia Bai Xue-Mei Qiu +1 位作者 Chun-Hong Xu Jian-Qiang Guo 《World Journal of Gastrointestinal Oncology》 SCIE 2024年第5期2123-2140,共18页
BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC... BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of GC.METHODS Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and cells.The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,respectively.Cell proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow cytometry.Expression of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western blot.Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system.Serpin family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining.The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis.The association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p.The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA.Overexpression of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 expression.Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression.Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2(ERK1/2).CONCLUSION This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC.MiR-145-5p was found to affect GC cell proliferation,migration,and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway. 展开更多
关键词 Gastric cancer MicroRNA-145-5p Serpin family E member 1 Epithelial-mesenchymal transition Proliferation Extracellular signal-regulated kinase-1/2
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自然杀伤细胞2组成员A、程序性死亡因子配体1表达检测对PD-L1阻断免疫治疗肌层浸润性膀胱癌反应性的预测价值
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作者 赵刚刚 张鸿毅 +3 位作者 肖克兵 杨辉 李子峰 赵华才 《陕西医学杂志》 CAS 2024年第2期252-256,共5页
目的:探究自然杀伤细胞2组成员A(NKG2A)及程序性死亡因子配体1(PD-L1)表达检测对PD-L1阻断免疫治疗肌层浸润性膀胱癌反应性的预测价值。方法:选取100例肌层浸润性膀胱癌患者作为研究对象,对其行PD-L1阻断免疫治疗后,根据治疗反应性将其... 目的:探究自然杀伤细胞2组成员A(NKG2A)及程序性死亡因子配体1(PD-L1)表达检测对PD-L1阻断免疫治疗肌层浸润性膀胱癌反应性的预测价值。方法:选取100例肌层浸润性膀胱癌患者作为研究对象,对其行PD-L1阻断免疫治疗后,根据治疗反应性将其分为缓解组和未缓解组;对缓解组患者随访3个月,将其分为复发组和未复发组。比较两组患者NKG2A和PD-L1在CD4^(+)和CD8^(+)上的表达水平,采用ROC曲线分析NKG2A和PD-L1预测膀胱癌患者治疗反应性的价值。结果:100例研究对象中,缓解组患者72例(72.00%),未缓解组患者28例(28.00%),两组性别、年龄比较无统计学差异(均P>0.05),但缓解组患者肿瘤直径小于未缓解组,NKG2A、PD-L1/CD4^(+)和PD-L1/CD8^(+)表达水平均低于未缓解组(均P<0.05)。膀胱癌患者NKG2A、PD-L1/CD4^(+)和PD-L1/CD8^(+)表达预测免疫治疗后缓解的AUC值分别为0.771、0.724、0.710;联合诊断的AUC为0.836。72例缓解患者中,出现复发29例(40.28%),未出现复发43例(59.72%),两组性别、年龄以及肿瘤直径比较无统计学差异(均P>0.05),但复发组NKG2A、PD-L1/CD4^(+)和PD-L1/CD8^(+)表达水平均高于未复发组(均P<0.05)。NKG2A、PD-L1/CD4^(+)和PD-L1/CD8^(+)表达预测膀胱癌患者缓解后复发的AUC值分别为0.775、0.740、0.728;联合诊断的AUC为0.874。结论:NKG2A、PD-L1/CD4^(+)和PD-L1/CD8^(+)在不同治疗反应性肌层浸润性膀胱癌患者外周血中表达水平不同,三者对于膀胱癌患者PD-L1阻断免疫治疗反应性均有一定的预测价值,且三者联合预测效能最佳。 展开更多
关键词 膀胱癌 肿瘤直径 自然杀伤细胞2组成员A 程序性死亡因子配体1 免疫治疗 反应性
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SLC3A2在慢性阻塞性肺病中的表达及其与炎症的关系
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作者 武小杰 李伟 +1 位作者 毛莉娜 杨硕 《内科急危重症杂志》 2024年第5期401-403,共3页
目的:探讨溶质转运载体家族3成员2(SLC3A2)在慢性阻塞性肺病(COPD)发生机制中的作用。方法:收集72例COPD稳定期患者纳入COPD组,另选取67例同期健康体检者为对照组。采集2组外周静脉血,通过密度梯度离心和红细胞裂解的方法分离出中性粒细... 目的:探讨溶质转运载体家族3成员2(SLC3A2)在慢性阻塞性肺病(COPD)发生机制中的作用。方法:收集72例COPD稳定期患者纳入COPD组,另选取67例同期健康体检者为对照组。采集2组外周静脉血,通过密度梯度离心和红细胞裂解的方法分离出中性粒细胞,采用蛋白免疫印迹法检测外周血中性粒细胞SLC3A2水平,酶联免疫吸附(ELISA)法检测血浆中白介素(IL)-8水平,同时收集2组的肺功能指标,包括第1秒用力呼气容积(FEV_(1))、用力肺活量(FVC)。分析SLC3A2与IL-8、FEV_(1)/FVC、FEV_(1)%预计值的相关性。结果:COPD组外周血中性粒细胞的SLC3A2及IL-8水平高于对照组(P均<0.01),SLC3A2与IL-8呈正相关(r=0.45,P<0.01),与FEV_(1)/FVC、FEV_(1)%预计值呈负相关(r=-0.42,-0.45,P均<0.01)。结论:SLC3A2可能通过炎症反应参与COPD的发生,SLC3A2有可能成为COPD临床的炎症标志物和治疗的靶点。 展开更多
关键词 慢性阻塞性肺病 溶质转运载体家族3成员2 氨基酸代谢 炎症机制
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基于miR-148a-3p/SMAD2轴探讨当归多糖对高糖诱导RGC凋亡的影响
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作者 王江涛 王艳新 +1 位作者 贾冠美 曹朗 《中国中医眼科杂志》 2024年第7期601-609,共9页
目的探究当归多糖(APS)对高糖诱导视网膜神经节细胞(RGC)凋亡的影响,及其基于微小RNA-148a-3p/Smad家族成员2(miR-148a-3p/SMAD2)轴的作用机制。方法将分别转染miR-148a-3p模拟物(mimics)、miR-148a-3p抑制剂(inhibitor)及其对照品mimic... 目的探究当归多糖(APS)对高糖诱导视网膜神经节细胞(RGC)凋亡的影响,及其基于微小RNA-148a-3p/Smad家族成员2(miR-148a-3p/SMAD2)轴的作用机制。方法将分别转染miR-148a-3p模拟物(mimics)、miR-148a-3p抑制剂(inhibitor)及其对照品mimics-NC、miR-NC的RGC,分为对照组(CG)、模型组(MG)、APS低剂量(APS-L)组、APS高剂量(APS-H)组、APS-H+miR-148a-3p对照品组(APS+miR-NC)、APS-H+miR-148a-3p抑制剂组(miR-148a-3p inhibitor),分别以相应的高糖和APS处理,采用实时荧光定量PCR(qRT-PCR)检测miR-148a-3p和SMAD2 mRNA表达水平,检测细胞活力、凋亡情况和氧化应激指标水平,Western Blot法检测SMAD2蛋白表达水平,双荧光素酶实验检测miR-148a-3p和SMAD2的靶向关系。结果(1)miR-148a-3p/SMAD2表达:APS-L组、APS-H组、APS-H+miR-NC组中miR-148a-3p表达水平均高于MG组(t_(APS-L)=6.564、t_(APS-H)=10.542、t_(APS-H+miR-NC)=9.945,均P=0.000),SMAD2 mRNA表达水平低于MG组(t_(APS-L)=4.147,P=0.004;t_(APS-H)=6.464、t_(APS-H+miR-NC)=6.586,均P=0.000);APS-H+miR-148a-3p inhibitor组miR-148a-3p表达水平低于APS-H+miRNC组(t=7.558,P=0.000),SMAD2 mRNA表达高于APS-H+miR-NC组(t=4.513,P=0.001),差异均有统计学意义。(2)细胞活力和凋亡率:APS-L组、APS-H组、APS-H+miR-NC组细胞活力高于MG组(t_(APS-L)=8.105、t_(APS-H)=11.509、t_(APS-H+miR-NC)=11.996,均P=0.000),细胞凋亡率低于MG组(t_(APS-L)=8.729、t_(APS-H)=15.690、t_(APS-H+miR-NC)=14.709,均P=0.000);APS-H+miR-148a-3p inhibitor组细胞活力低于APS-H+miR-NC组(t=10.212,P=0.000),细胞凋亡率高于APS-H+miR-NC组(t=12.247,P=0.000),差异均有统计学意义。(3)氧化应激:APS-L组、APS-H组、APS-H+miR-NC组乳酸脱氢酶(LDH)和丙二醛(MDA)均低于MG组(LDH:t_(APS-L)=11.257、t_(APS-H)=18.770、t_(APS-H+miR-NC)=18.364,均P=0.000;MDA:t_(APS-L)=11.121、t_(APS-H)=17.139、t_(APS-H+miR-NC)=17.768,均P=0.000),超氧化物歧化酶(SOD)和谷胱甘肽(GSH)均高于MG组(SOD:t_(APS-L)=9.408、t_(APS-H)=14.833、t_(APS-H+miR-NC)=13.240,均P=0.000;GSH:t_(APS-L)=5.616、t_(APS-H)=12.080、t_(APS-H+miR-NC)=12.642,均P=0.000);APS-H+miR-148a-3p inhibitor组LDH和MDA均高于APS-H+miR-NC组(t_(LDH)=15.121、t_(MDA)=14.613,均P=0.000),SOD和GSH均低于APS-H+miR-NC组(tSOD=12.278、tGSH=8.912,均P=0.000),差异均有统计学意义。。(4)凋亡蛋白:APS-L组、APS-H组和APS-H+miR-NC组SMAD2、Bcl-2相关X蛋白(Bax)和半胱天冬酶-3(Caspase-3)表达低于MG组(SMAD2:t_(APS-L)=4.565、t_(APS-H)=8.042、t_(APS-H+miR-NC)=7.390,均P=0.000;Bax:t_(APS-L)=4.916、t_(APS-H)=8.763、t_(APS-H+miR-NC)=8.336,均P=0.000;Caspase-3:t_(APS-L)=4.214、t_(APS-H)=10.201、t_(APS-H+miR-NC)=9.536,均P=0.000),B细胞淋巴瘤-2(Bcl-2)表达高于MG组(t_(APS-L)=3.713,P=0.001;t_(APS-H)=10.108、t_(APS-H+miR-NC)=10.314,均P=0.000);APS-H+miR-148a-3p inhibitor组SMAD2、Bax、Caspase-3表达均高于APS-H+miR-NC组(t_(SMAD2)=5.651、t_(Bax)=6.840、t_(Caspase-3)=8.205,均P=0.000),Bcl-2表达低于APS-H+miR-NC组(t=9.283,P=0.000),差异均有统计学意义。(5)靶向关系:miR-148a-3p与SMAD2的3'非翻译区存在结合位点。miR-148a-3p mimics和野生型SMAD2共转染组荧光素酶活性低于mimics-NC和野生型SMAD2共转染组,差异有统计学意义(t=12.781,P=0.000)。结论当归多糖可能通过上调miR-148a-3p、下调SMAD2,改善高糖诱导的RGC凋亡和氧化应激损伤。 展开更多
关键词 当归多糖 视网膜神经节细胞 微小RNA-148a-3p SMAD家族成员2
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垂体泌乳素瘤患者组织NR2C2、EMMPRIN水平变化及其与肿瘤侵袭性、临床预后的关系探讨
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作者 洪艳 陈静雅 胡影 《齐齐哈尔医学院学报》 2024年第7期628-631,共4页
目的探讨垂体泌乳素瘤组织中核受体亚家族2c成员2(NR2C2)和细胞外基质金属蛋白酶诱导因子(EMMPRIN)的水平变化及其与肿瘤侵袭性、临床预后的关系。方法选择2019年6月—2021年6月本院收治的78例垂体泌乳素瘤患者为研究对象,患者均行手术... 目的探讨垂体泌乳素瘤组织中核受体亚家族2c成员2(NR2C2)和细胞外基质金属蛋白酶诱导因子(EMMPRIN)的水平变化及其与肿瘤侵袭性、临床预后的关系。方法选择2019年6月—2021年6月本院收治的78例垂体泌乳素瘤患者为研究对象,患者均行手术切除,术后随访时间1年。采用免疫组化法检测NR2C2和EMMPRIN表达情况,对比癌组织、癌旁组织中NR2C2和EMMPRIN表达,分析垂体泌乳素瘤患者癌组织中NR2C2和EMMPRIN表达情况与临床病理参数的关系,分析影响垂体泌乳素瘤患者预后的因素。结果癌组织中NR2C2阳性表达率高于癌旁组织(P<0.05),EMMPRIN阳性表达率低于癌旁组织(P<0.05),NR2C2、EMMPRIN表达均是预后不良的独立危险因素(P<0.05);受试者工作特征曲线(ROC)分析显示,垂体泌乳素瘤组织NR2C2、EMMPRIN两者联合预测垂体泌乳素瘤患者预后不良的曲线下面积(AUC)为0.886,高于NR2C2、EMMPRIN单独预测的AUC(Z=5.245,P=0.014;Z=3.652,P=0.028)。结论垂体泌乳素瘤患者癌组织中NR2C2和EMMPRIN表达与肿瘤侵袭性、临床预后有关,NR2C2阳性患者预后不良风险高。 展开更多
关键词 垂体泌乳素瘤 核受体亚家族2c成员2 EMMPRIN 免疫组化法
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PIM1基因对急性髓系白血病U937细胞增殖、凋亡及JAK2/STAT3信号通路的影响
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作者 高鑫 储李婧 颜宗海 《中国实验血液学杂志》 CAS CSCD 北大核心 2024年第3期663-669,共7页
目的:探讨PIM1基因对急性髓系白血病(AML)U937细胞增殖、凋亡的影响,以及对JAK2/STAT3通路的调控作用。方法:收集初诊成人AML患者和单纯缺铁性贫血患者的骨髓单个核细胞,荧光定量PCR检测PIM1 mRNA表达。将AML细胞系U937细胞分为:U937组(... 目的:探讨PIM1基因对急性髓系白血病(AML)U937细胞增殖、凋亡的影响,以及对JAK2/STAT3通路的调控作用。方法:收集初诊成人AML患者和单纯缺铁性贫血患者的骨髓单个核细胞,荧光定量PCR检测PIM1 mRNA表达。将AML细胞系U937细胞分为:U937组(U937细胞正常培养)、Si-PIM1组(U937细胞转染含PIM1 mRNA的低表达腺病毒载体)、Si-NC组(U937细胞转染不含PIM1 mRNA的低表达腺病毒载体)、CoA1组(U937细胞中加入浓度为20μmol/L的JAK2激活剂CoA1)、Si-PIM1+CoA1组(U937细胞转染含PIM1 mRNA低表达的腺病毒载体并加入浓度为20μmol/L的CoA1)。培养24 h。荧光定量PCR和蛋白印迹法检测U937细胞PIM1 mRNA和蛋白、JAK2/STAT3通路、细胞周期、凋亡相关蛋白表达;噻唑蓝法检测细胞增殖活性;流式细胞术检测细胞周期变化及凋亡率。结果:AML患者骨髓单个核细胞中PIM1 mRNA表达水平高于单纯缺铁性贫血患者(P<0.05)。与U937组相比,Si-PIM1组细胞PIM1 mRNA和蛋白、p-JAK2/JAK2、p-STAT3/STAT3、Cyclin D1、CDK2蛋白、细胞增殖活性、S期比例、G2/M期比例降低(均P<0.05),p27、Caspase-3蛋白、G0/G1期、凋亡率升高(均P<0.05),而CoA1组上述指标的变化情况与Si-PIM1组正好相反,CoA1可逆转Si-PIM1对U937细胞的作用效果。U937组、Si-PIM1+CoA1组、Si-NC组U937细胞上述指标差异无统计学意义(P>0.05)。结论:敲低PIM1基因表达可抑制U937细胞增殖、促进凋亡,缓解ALM进程,且上述作用可能与抑制JAK2/STAT3通路活化有关。 展开更多
关键词 丝/苏氨酸激酶家族成员1 急性髓系白血病U937细胞 增殖 凋亡 Janus酪氨酸激酶2/信号转导及转录激活因子3通路
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Cycles of fine-grained sedimentation and their influences on organic matter distribution in the second member of Paleogene Kongdian Formation in Cangdong Sag,Bohai Bay Basin,East China
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作者 ZHAO Xianzheng PU Xiugang +10 位作者 YAN Jihua JIN Fengming SHI Zhannan CHAI Gongquan HAN Wenzhong LIU Yan JIANG Wenya CHEN Changwei ZHANG Wei FANG Zheng XIE Delu 《Petroleum Exploration and Development》 SCIE 2023年第3期534-546,共13页
According to the theory of sequence stratigraphy based on continental transgressive-regressive(T-R)cycles,a 500 m continuous core taken from the second member of Kongdian Formation(Kong 2 Member)of Paleogene in Well G... According to the theory of sequence stratigraphy based on continental transgressive-regressive(T-R)cycles,a 500 m continuous core taken from the second member of Kongdian Formation(Kong 2 Member)of Paleogene in Well G108-8 in the Cangdong Sag,Bohai Bay Basin,was tested and analyzed to clarify the high-frequency cycles of deep-water fine-grained sedimentary rocks in lacustrine basins.A logging vectorgraph in red pattern was plotted,and then a sequence stratigraphic framework with five-order high-frequency cycles was formed for the fine-grained sedimentary rocks in the Kong 2 Member.The high-frequency cycles of fine-grained sedimentary rocks were characterized by using different methods and at different scales.It is found that the fifth-order T cycles record a high content of terrigenous clastic minerals,a low paleosalinity,a relatively humid paleoclimate and a high density of laminae,while the fifth-order R cycles display a high content of carbonate minerals,a high paleosalinity,a dry paleoclimate and a low density of laminae.The changes in high-frequency cycles controlled the abundance and type of organic matter.The T cycles exhibit relatively high TOC and abundant endogenous organic matters in water in addition to terrigenous organic matters,implying a high primary productivity of lake for the generation and enrichment of shale oil. 展开更多
关键词 fine-grained sediment high-frequency cycle lamina density organic matter Paleogene kong 2 member Cangdong Sag Bohai Bay Basin
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Solute carrier family 2 members 1 and 2 as prognostic biomarkers in hepatocellular carcinoma associated with immune infiltration 被引量:2
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作者 Qing Peng Li-Yuan Hao +7 位作者 Ying-Lin Guo Zhi-Qin Zhang Jing-Min Ji Yu Xue Yi-Wei Liu Jun-Lan Lu Cai-Ge Li Xin-Li Shi 《World Journal of Clinical Cases》 SCIE 2022年第13期3989-4019,共31页
BACKGROUND Metabolic reprogramming has been identified as a core hallmark of cancer.Solute carrier family 2 is a major glucose carrier family.It consists of 14 members,and we mainly study solute carrier family 2 membe... BACKGROUND Metabolic reprogramming has been identified as a core hallmark of cancer.Solute carrier family 2 is a major glucose carrier family.It consists of 14 members,and we mainly study solute carrier family 2 member 1(SLC2A1)and solute carrier family 2 member 2(SLC2A2)here.SLC2A1,mainly existing in human erythrocytes,brain endothelial cells,and normal placenta,was found to be increased in hepatocellular carcinoma(HCC),while SLC2A2,the major transporter of the normal liver,was decreased in HCC.AIM To identify if SLC2A1 and SLC2A2 were associated with immune infiltration in addition to participating in the metabolic reprogramming in HCC.METHODS The expression levels of SLC2A1 and SLC2A2 were tested in HepG2 cells,HepG215 cells,and multiple databases.The clinical characteristics and survival data of SLC2A1 and SLC2A2 were examined by multiple databases.The correlation between SLC2A1 and SLC2A2 was analyzed by multiple databases.The functions and pathways in which SLC2A1,SLC2A2,and frequently altered neighbor genes were involved were discussed in String.Immune infiltration levels and immune marker genes associated with SLC2A1 and SLC2A2 were discussed from multiple databases.RESULTS The expression level of SLC2A1 was up-regulated,but the expression level of SLC2A2 was down-regulated in HepG2 cells,HepG215 cells,and liver cancer patients.The expression levels of SLC2A1 and SLC2A2 were related to tumor volume,grade,and stage in HCC.Interestingly,the expression levels of SLC2A1 and SLC2A2 were negatively correlated.Further,high SLC2A1 expression and low SLC2A2 expression were linked to poor overall survival and relapse-free survival.SLC2A1,SLC2A2,and frequently altered neighbor genes played a major role in the occurrence and development of tumors.Notably,SLC2A1 was positively correlated with tumor immune infiltration,while SLC2A2 was negatively correlated with tumor immune infiltration.Particularly,SLC2A2 methylation was positively correlated with lymphocytes.CONCLUSION SLC2A1 and SLC2A2 are independent therapeutic targets for HCC,and they are quintessential marker molecules for predicting and regulating the number and status of immune cells in HCC. 展开更多
关键词 Hepatocellular carcinoma Solute carrier family 2 member 1 Solute carrier family 2 member 2 PROGnoSTIC Immune infiltration
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结直肠癌组织中NR2F1的表达及其与预后的相关性
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作者 陈汝蕾 沈铭红 +2 位作者 王凤 居颂文 吕京澴 《海南医学》 CAS 2024年第7期968-972,共5页
目的检测结直肠癌中核受体亚家族2组F成员1(NR2F1)的蛋白表达水平,并探讨其与患者预后的关系。方法选择2012年8月至2013年9月在苏州市立医院进行根治性切除术的56例结直肠癌患者作为研究对象,采集患者的结直肠癌组织标本及对应的癌旁组... 目的检测结直肠癌中核受体亚家族2组F成员1(NR2F1)的蛋白表达水平,并探讨其与患者预后的关系。方法选择2012年8月至2013年9月在苏州市立医院进行根治性切除术的56例结直肠癌患者作为研究对象,采集患者的结直肠癌组织标本及对应的癌旁组织标本。采用EnVision法测定结直肠癌组织和癌旁组织的NR2F1的蛋白表达水平,比较不同NR2F1蛋白表达水平结直肠癌患者的临床病理特征。采用Kaplan-Meier法绘制结直肠癌患者的生存曲线,分析NR2F1蛋白表达水平与结直肠癌的预后的相关性。结果结直肠癌组织的NR2F1高表达率为48.21%,明显高于癌旁组织的7.14%,差异有统计学意义(P<0.05);NR2F1高表达者的无脉管侵犯率为85.19%,明显高于NR2F1低表达者的58.62%,差异有统计学意义(P<0.05);NR2F1高表达患者突破浆膜层的占比为48.15%,明显低于NR2F1低表达者的65.52%,且随着浸润深度从固有肌层到突破浆膜层,NR2F1低表达增加,差异均具有统计学意义(P<0.05);NR2F1高表达和低表达患者在性别、年龄、肿块大小、分化程度、淋巴结转移方面比较,差异均无统计学意义(P>0.05);经Kaplan-Meier生存曲线分析结果显示,结直肠癌的NR2F1高表达患者的10年总生存率为26.79%,明显高于NR2F1低表达患者的17.86%,差异有统计学意义(P<0.05)。结论结直肠癌的NR2F1表达升高,NR2F1可能参与了结直肠癌的发生、侵袭,对患者的预后造成一定的影响。 展开更多
关键词 结直肠癌 核受体亚家族2组F成员1 侵袭 预后
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溶质载体家族3成员2表达与双硫死亡、铁死亡及肿瘤关系的研究进展
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作者 马欢 代九菊 +1 位作者 杨艳丽 周祖邦 《中国病理生理杂志》 CAS CSCD 北大核心 2024年第9期1772-1776,共5页
铁死亡和双硫死亡与多种疾病相关。铁死亡的特征是铁离子和脂质活性氧的异常累积,而双硫死亡则是二硫化物的异常累积。溶质载体家族3成员2(SLC3A2)作为溶质载体家族的一员,不仅参与调控肿瘤细胞的增殖、迁移、侵袭和凋亡,还参与细胞铁... 铁死亡和双硫死亡与多种疾病相关。铁死亡的特征是铁离子和脂质活性氧的异常累积,而双硫死亡则是二硫化物的异常累积。溶质载体家族3成员2(SLC3A2)作为溶质载体家族的一员,不仅参与调控肿瘤细胞的增殖、迁移、侵袭和凋亡,还参与细胞铁死亡和双硫死亡,在肿瘤的发生发展中起关键作用。本文阐述了SLC3A2与双硫死亡、铁死亡和肿瘤关系的研究进展,旨在为癌症靶向治疗提供理论基础。 展开更多
关键词 溶质载体家族3成员2 双硫死亡 铁死亡 肿瘤
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SCNH2 is a novel apelinergic family member acting as a potent mitogenic and chemotactic factor for both endothelial and epithelial cells 被引量:1
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作者 Changge Fang Ingalill Avis +11 位作者 Caterina Bianco Natalie Held Jennifer Morris Kris Ylaya Stephen M. Hewitt Alfred C. Aplin Roberto F. Nicosia Laura A. Fung John D. Lewis William G. Stetler-Stevenson David S. Salomon Frank Cuttitta 《Open Journal of Clinical Diagnostics》 2013年第2期37-51,共15页
The gut hormone apelin is a major therapeutic focus for several diseases involving inflammation and aberrant cell growth. We investigated whether apelin-36 contained alternative bioactive peptides associated with norm... The gut hormone apelin is a major therapeutic focus for several diseases involving inflammation and aberrant cell growth. We investigated whether apelin-36 contained alternative bioactive peptides associated with normal physiology or disease. Amino acid sequence analysis of apelin-36 identified an amidation motif consistent with the formation of a secondary bioactive peptide (SCNH2). SCNH2 is proven to be mitogenic and chemotactic in normal/malignant cells and augments angiogenesis via a PTX-resistant/CT-X-sensitive G protein-coupled receptor (GPCR). Notably, SCNH2 is substantially more potent and sensitive than apelin-13 and vascular endothelial growth factor-A. Endogenous SCNH2 is highly expressed in human tumors and placenta and in mouse embryonic tissues. Our findings demonstrate that SCNH2 is a new apelinergic member with critical pluripotent roles in angiogenesis related diseases and embryogenesis via a non-APJ GPCR. 展开更多
关键词 noVEL Apelinergic member SCNH2 Angiogenesis Migration EMBRYOGENESIS
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三磷酸腺苷结合盒转运蛋白G2与痛风病关联的病理机制研究进展
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作者 韩宇 黄锦坚 +2 位作者 林志健 张冰 王雨 《世界中医药》 CAS 北大核心 2024年第3期437-443,共7页
痛风病是指与高尿酸血症、尿酸盐沉积(关节、肾脏)等尿酸代谢紊乱密切相关的进展性代谢疾病,根据其病理进展特点和临床表现,其病程可分为高尿酸血症阶段、尿酸盐沉积阶段、痛风性炎症阶段。三磷酸腺苷结合盒转运蛋白G2(ABCG2)是高通量... 痛风病是指与高尿酸血症、尿酸盐沉积(关节、肾脏)等尿酸代谢紊乱密切相关的进展性代谢疾病,根据其病理进展特点和临床表现,其病程可分为高尿酸血症阶段、尿酸盐沉积阶段、痛风性炎症阶段。三磷酸腺苷结合盒转运蛋白G2(ABCG2)是高通量的尿酸转运体,既参与了机体尿酸外排的肠-肾途径,又与痛风性炎症密切相关。通过切入ABCG2,对痛风病病理机制研究进展进行综述,以期为临床痛风病的深入研究及防治提供新的见解。 展开更多
关键词 三磷酸腺苷结合盒转运蛋白G2 痛风病 高尿酸血症 痛风性关节炎 尿酸盐沉积 尿酸代谢 病理机制 研究进展
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自然杀伤细胞家族2成员D受体-配体轴在血液瘤中的作用研究进展
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作者 刘婕 陈抒鹏 +1 位作者 章美玲 曾英坚 《陕西医学杂志》 CAS 2024年第9期1286-1289,F0003,共5页
自然杀伤细胞家族2成员D(NKG2D)受体通过表达在自然杀伤(NK)细胞和细胞毒性T淋巴(CTLs)细胞上激活这些免疫细胞对抗肿瘤。肿瘤细胞通过降低自然杀伤细胞家族2成员D配体(NKG2DLs)的表达来逃避免疫系统的监视,从而促进肿瘤的免疫逃逸。最... 自然杀伤细胞家族2成员D(NKG2D)受体通过表达在自然杀伤(NK)细胞和细胞毒性T淋巴(CTLs)细胞上激活这些免疫细胞对抗肿瘤。肿瘤细胞通过降低自然杀伤细胞家族2成员D配体(NKG2DLs)的表达来逃避免疫系统的监视,从而促进肿瘤的免疫逃逸。最新的研究揭示了NKG2D受体-配体轴在血液瘤的发展、免疫监视和治疗中的关键作用,尤其是在阐明免疫逃逸机制和开发新的治疗策略方面显示出巨大潜力。现从NKG2D受体-配体轴在血液瘤发病机制、免疫监测及治疗中的作用进行阐述,在加深对血液瘤病理机制理解的同时,为提升治疗效果开辟了新的策略。 展开更多
关键词 血液瘤 自然杀伤2组成员D受体 自然杀伤2组成员D配体 免疫逃逸 治疗靶点 靶向药物
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鄂尔多斯盆地铁边城地区长2油层组剩余油模拟
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作者 张晓明 吴勤博 +5 位作者 邹焰 王皓立 韩明 郭龙飞 狄晓磊 屈乐 《科学技术与工程》 北大核心 2024年第5期1799-1807,共9页
为了实现油田增储上产及老井挖潜的目标,提升剩余油资源开发潜力,通过岩心、薄片、电镜、物性、模拟方法系统的研究了鄂尔多斯盆地西北部姬塬油田铁边城地区长2段主力油层的剩余油分布特征。研究显示,长2_(1)^(3-2)和长2_(1)^(3-3)小层... 为了实现油田增储上产及老井挖潜的目标,提升剩余油资源开发潜力,通过岩心、薄片、电镜、物性、模拟方法系统的研究了鄂尔多斯盆地西北部姬塬油田铁边城地区长2段主力油层的剩余油分布特征。研究显示,长2_(1)^(3-2)和长2_(1)^(3-3)小层为主力产油层,平均厚度分别为12.2 m及11.1 m。目的层砂岩储层的孔隙度通常介于12%~18%,渗透率则通常低于8 mD。根据相控原则,建立了主力产层的物理属性模型及流体模型;进而,开展了剩余油分布数值模拟研究。通过基于实测产水及产油量约束的历史生产曲线拟合,获得了剩余油的纵横向分布结果。研究显示,剩余油分布受砂体边界、物性差异及注采关系的影响。剩余油整体上成片分布;但是,受油藏物性差异的影响,注水多呈不均匀受效,因而造成局部剩余油富集。剩余油主要分布在砂体边界处,这些区域无井网控制,因而水驱程度低,剩余油分布较多。受长期注采的影响,井间会形成高渗区,这些其余类似高速通道,会发生快速水淹,其周边则形成剩余油滞留区。可见,剩余油富集明显受微相、物性、注水及井网因素的控制。 展开更多
关键词 鄂尔多斯盆地 2 三维模型 数值模拟 剩余油
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雄黄主要成分As_(2)S_(2)通过“ANP32A-INHAT-H3乙酰化”轴抑制三阴性乳腺癌细胞增殖、迁移的表观遗传调控机制
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作者 孙杰杰 张素峰 +1 位作者 王曼曼 李庆林 《安徽中医药大学学报》 CAS 2024年第3期86-92,共7页
目的探究雄黄主要成分二硫化二砷(As_(2)S_(2))对三阴性乳腺癌(triple negative breast cancer,TNBC)的作用及表观遗传调控机制。方法采用CCK-8、平板克隆形成和细胞划痕实验探究As_(2)S_(2)对人正常乳腺上皮细胞MCF-10A及TNBC细胞增殖... 目的探究雄黄主要成分二硫化二砷(As_(2)S_(2))对三阴性乳腺癌(triple negative breast cancer,TNBC)的作用及表观遗传调控机制。方法采用CCK-8、平板克隆形成和细胞划痕实验探究As_(2)S_(2)对人正常乳腺上皮细胞MCF-10A及TNBC细胞增殖和迁移的影响;4D-label free定量蛋白质组学分析挖掘As_(2)S_(2)抗TNBC的潜在干预靶点酸性核磷蛋白家族成员32A(acidic nuclear phosphoprotein family member 32A,ANP32A);慢病毒感染法构建ANP32A过表达敲低细胞株,探究潜在靶点ANP32A对As_(2)S_(2)抗TNBC作用的影响;蛋白质免疫共沉淀和Western blot实验探究As_(2)S_(2)是否通过ANP32A调控TNBC细胞H3乙酰化。结果As_(2)S_(2)对人正常乳腺上皮细胞MCF-10A影响甚微,但显著抑制TNBC细胞增殖和迁移,且呈剂量依赖性;4D-lable free定量蛋白质组学分析结果显示,促癌因子ANP32A被As_(2)S_(2)显著下调,且ANP32A表达影响As_(2)S_(2)在TNBC中的抗增殖和迁移效果。As_(2)S_(2)能下调ANP32A的蛋白水平,抑制乙酰转移酶抑制剂复合物亚基的招募,增加H3乙酰化水平。结论As_(2)S_(2)通过下调ANP32A蛋白调控TNBC细胞中H3乙酰化,抑制TNBC细胞增殖和迁移。 展开更多
关键词 雄黄 二硫化二砷 酸性核磷蛋白家族成员32A H3乙酰化 表观遗传 三阴性乳腺癌
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血清SLC7A11、JAK2水平与急性非静脉曲张性上消化道出血严重程度及预后的关系
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作者 毛晓琴 郑爱华 +1 位作者 何盛琴 张珊 《国际检验医学杂志》 CAS 2024年第20期2461-2466,共6页
目的探讨血清溶质载体家族7成员11(SLC7A11)、Janus激酶2(JAK2)水平与急性非静脉曲张性上消化道出血(ANVUGIB)严重程度及预后的关系。方法选取2019年4月至2023年4月于该院接受治疗的108例ANVUGIB患者作为研究对象,根据ANVUGIB严重程度... 目的探讨血清溶质载体家族7成员11(SLC7A11)、Janus激酶2(JAK2)水平与急性非静脉曲张性上消化道出血(ANVUGIB)严重程度及预后的关系。方法选取2019年4月至2023年4月于该院接受治疗的108例ANVUGIB患者作为研究对象,根据ANVUGIB严重程度分为重度组(31例)、中度组(44例)、轻度组(33例)。根据患者预后分为预后不良组(41例)和预后良好组(67例)。另选取同期在该院进行体检的健康志愿者50例为对照组。采用酶联免疫吸附试验检测血清SLC7A11、JAK2水平,Spearman相关分析血清SLC7A11、JAK2水平与Framingham风险(FRS)、格拉斯哥-布拉奇福德出血(GBS)评分的相关性,多因素Logistic回归分析ANVUGIB患者预后不良的影响因素,受试者工作特征(ROC)曲线分析血清SLC7A11、JAK2对ANVUGIB患者预后不良的预测价值。结果3组不同严重程度的ANVUGIB患者血清SLC7A11水平均低于对照组,血清JAK2水平均高于对照组(均P<0.05)。随着病情严重程度增加,血清SLC7A11水平逐渐降低,血清JAK2水平及FRS、GBS评分逐渐升高(均P<0.05)。ANVUGIB患者血清SLC7A11水平与FRS、GBS评分均呈负相关,血清JAK2水平与FRS、GBS评分均呈正相关(均P<0.05)。预后不良组出血量>400 mL的患者占比、红细胞分布宽度、FRS评分、GBS评分、JAK2水平均高于预后良好组,血红蛋白、SLC7A11水平低于预后良好组(P<0.05)。出血量>400 mL、JAK2水平升高是ANVUGIB患者预后不良的危险因素,SLC7A11水平升高是保护因素(均P<0.05)。血清SLC7A11、JAK2联合预测ANVUGIB患者预后不良的曲线下面积优于各指标单独预测(Z_(二者联合-SLC7A11)=3.086、Z_(二者联合-JAK2)=2.330,P=0.020、0.030)。结论ANVUGIB患者血清SLC7A11水平降低、JAK2水平升高,可有效评估患者病情严重程度及预后,二者联合预测患者预后具有更高效能。 展开更多
关键词 溶质载体家族7成员11 JANUS激酶2 急性非静脉曲张性上消化道出血 预后
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茯苓酸通过调节Nrf2/SLC7A11/GPX4信号通路抑制氧糖剥夺/复氧诱导的心肌细胞铁死亡 被引量:1
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作者 王飞飞 陈伯艳 李琼 《中西医结合心脑血管病杂志》 2024年第2期267-273,共7页
目的:探究茯苓酸通过调节核因子E2相关因子2(Nrf2)/溶质载体家族7成员11(SLC7A11)/谷胱甘肽过氧化物酶4(GPX4)信号通路抑制氧糖剥夺/复氧(OGD/R)诱导的心肌细胞铁死亡的机制。方法:体外培养大鼠心肌细胞H9c2,诱导建立细胞OGD/R模型后以0... 目的:探究茯苓酸通过调节核因子E2相关因子2(Nrf2)/溶质载体家族7成员11(SLC7A11)/谷胱甘肽过氧化物酶4(GPX4)信号通路抑制氧糖剥夺/复氧(OGD/R)诱导的心肌细胞铁死亡的机制。方法:体外培养大鼠心肌细胞H9c2,诱导建立细胞OGD/R模型后以0、1.0、2.5、5.0、10.0、20.0μmol/L茯苓酸处理24 h,通过细胞计数试剂盒-8(CCK-8)法检测各处理组细胞活力后筛选出合适的茯苓酸作用浓度。将H9c2细胞随机分为对照组、模型组、茯苓酸组、ML385组(Nrf2抑制剂组)、茯苓酸+ML385组,除对照组外其余各组建立细胞OGD/R模型后以茯苓酸、ML385分组处理,采用CCK-8法与流式细胞实验分别检测各组H9c2细胞活力、凋亡率;采用试剂盒检测各组H9c2细胞培养基上清中乳酸脱氢酶(LDH)、促炎因子[前列腺素E2(PGE2)、肿瘤坏死因子-α(TNF-α)]、抗炎因子白细胞介素(IL)-10水平及细胞抗氧化因子[过氧化氢酶(CAT)、谷胱甘肽(GSH)]、铁死亡相关指标[铁含量、丙二醛(MDA)]水平;采用免疫印迹实验检测各组H9c2细胞凋亡及Nrf2/SLC7A11/GPX4信号通路相关蛋白表达。结果:与对照组比较,模型组细胞凋亡率、LDH释放量、细胞培养基上清中PGE2及TNF-α水平、细胞铁含量、MDA水平及Bax、Caspase-3蛋白表达均升高(P<0.05),细胞活力、细胞培养基上清中IL-10水平、细胞CAT及GSH水平、Bcl-2及Nrf2、SLC7A11、GPX4蛋白表达降低(P<0.05)。与模型组比较,茯苓酸组细胞凋亡率、LDH释放量、细胞培养基上清中PGE2及TNF-α水平、细胞铁含量、MDA水平及Bax、Caspase-3蛋白表达均降低(P<0.05),细胞活力、细胞培养基上清中IL-10水平、细胞CAT及GSH水平、Bcl-2及Nrf2、SLC7A11、GPX4蛋白表达升高(P<0.05);ML385组细胞凋亡率、LDH释放量、细胞培养基上清中PGE2及TNF-α水平、细胞铁含量、MDA水平及Bax、Caspase-3蛋白表达均升高(P<0.05),细胞活力、细胞培养基上清中IL-10水平、细胞CAT及GSH水平、Bcl-2及Nrf2、SLC7A11、GPX4蛋白表达降低(P<0.05)。与茯苓酸组比较,茯苓酸+ML385组细胞凋亡率、LDH释放量、细胞培养基上清中PGE2及TNF-α水平、细胞铁含量、MDA水平及Bax、Caspase-3蛋白表达均升高(P<0.05),细胞活力、细胞培养基上清中IL-10水平、细胞CAT及GSH水平、Bcl-2及Nrf2、SLC7A11、GPX4蛋白表达降低(P<0.05)。结论:茯苓酸可通过激活Nrf2/SLC7A11/GPX4信号而抑制OGD/R诱导的心肌细胞炎症、脂质过氧化与铁死亡,增强其抗氧化活性及细胞活力,最终减轻其细胞凋亡损伤。 展开更多
关键词 氧糖剥夺/复氧 心肌细胞 茯苓酸 核因子E2相关因子2/溶质载体家族7成员11/谷胱甘肽过氧化物酶4 铁死亡 实验研究
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Heavy minerals clustering analysis in application of provenance analysis of Kong 2 Member in Kongnan area
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作者 Narenna WU 《Global Geology》 2007年第1期44-47,共4页
The main task of provenance analysis is to determine the source of sediments and the position of parent rocks.Provenance analysis may find out the relationship between erosion districts and sediment zone,between the u... The main task of provenance analysis is to determine the source of sediments and the position of parent rocks.Provenance analysis may find out the relationship between erosion districts and sediment zone,between the uplift and the depression in the process of basin development.The authors use the method of heavy mineral clustering analysis and estimate the provenance direction of Huanghua Depression in the Paleogene Kong 2 Member.Research shows that there were five provenance areas of Kong 2 Member in Kongnan area.They are western(Shenusi),northwestern(Cangzhou),eastern(Ganhuatun),northeastern and southeastern.The main provenance areas were northwestern and western,while the southern provenance could not be ruled out.And these areas are consistent with the known provenance areas. 展开更多
关键词 stable heavy minerals clustering analysis provenance analysis kongnan area kong 2 member
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