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Aldo-keto reductase family member C3(AKR1C3)promotes hepatocellular carcinoma cell growth by producing prostaglandin F2α
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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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Artesunate Effect on Schistosome Thioredoxin Glutathione Reductase and Cytochrome c Peroxidase as New Molecular Targets in Schistosoma mansoni-infected Mice 被引量:2
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作者 Amany A.Abdin Dalia S.Ashour Zeinab S.Shoheib 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2013年第12期953-961,共9页
Objective To investigate the possible effect of artesunate (ART) on schistosome thioredoxin glutathione reductase (TGR) and cytochrome c peroxidase (CcP) in Schistosoma mansoni-infected mice. Methods A total of ... Objective To investigate the possible effect of artesunate (ART) on schistosome thioredoxin glutathione reductase (TGR) and cytochrome c peroxidase (CcP) in Schistosoma mansoni-infected mice. Methods A total of 200 laboratory bred male Swiss albino mice were divided into 4 groups (50 mice in each group). Group I: infected untreated group (Control group) received a vehicle of 1% sodium carbonyl methylcellulose (CMC-Na); Group II: infected then treated with artesunate; Group III infected then treated with praziquantel, and group IV: infected then treated with artesunate then praziquantel. Adult S. mansoni worms were collected by Animal Perfusion Method, tissue egg counted, TGR, and CcP mRNA Expression were estimated of in $. mansoni adult worms by semi-quantitative rt-PCR. Results Semi-quantitative rt-PCR values revealed that treatment with artesunate caused significant decrease in expression of schistosome TGR and CcP in comparison to the untreated group. In contrast, the treatment with praziquantel did not cause significant change in expression of these genes. The results showed more reduction in total worm and female worm count in combined ART-PZQ treated group than in monotherapy treated groups by either ART or PZO, Moreover, complete disappearance (100%) of tissue eggs was recorded in ART-PZQ treated group with a respective reduction rate of 95.9% and 68.4% in ART- and PZQ-treated groups. Conclusion The current study elucidated for the first time that anti-schistosomal mechanisms of artesunate is mediated via reduction in expression of schistosome TGR and CcP. Linking these findings, addition of artesunate to praziquantel could achieve complete cure outcome in treatment of schistosomiasis. 展开更多
关键词 SCHISTOSOMIASIS ARTESUNATE PRAZIQUANTEL thioredoxin glutathione reductase Cytochrome c peroxidase
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Thioredoxin and glutaredoxin-mediated redox regulation of ribonucleotide reductase 被引量:6
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作者 Rajib Sengupta Arne Holmgren 《World Journal of Biological Chemistry》 CAS 2014年第1期68-74,共7页
Ribonucleotide reductase(RNR), the rate-limitingenzyme in DNA synthesis, catalyzes reduction of thedifferent ribonucleotides to their corresponding deoxyri-bonucleotides. The crucial role of RNR in DNA synthesishas ma... Ribonucleotide reductase(RNR), the rate-limitingenzyme in DNA synthesis, catalyzes reduction of thedifferent ribonucleotides to their corresponding deoxyri-bonucleotides. The crucial role of RNR in DNA synthesishas made it an important target for the development ofantiviral and anticancer drugs. Taking account of the re-cent developments in this field of research, this reviewfocuses on the role of thioredoxin and glutaredoxin sys-tems in the redox reactions of the RNR catalysis. 展开更多
关键词 Ribonucleotide reductase thioredoxin GLUTAREDOXIN DNA synthesis THIOL DISULFIDES REPLICATION
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Is thioredoxin reductase involved in the defense againsi DNA fragmentation in varicocele? 被引量:1
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作者 Gill Ozdemirler Erata Canan Kfiqiikgergin +3 位作者 Giilsan Aktan Ates KadoOuI Miijdat Uysal Necla Kocak-Toker 《Asian Journal of Andrology》 SCIE CAS CSCD 2013年第4期518-522,I0009,共6页
We aimed to investigate the role of thioredoxin reductase (TR) and inducible heat shock protein 70 (iHsp70) and their relationship with sperm quality in varicocele (VAR) patients. Semen samples were obtained fro... We aimed to investigate the role of thioredoxin reductase (TR) and inducible heat shock protein 70 (iHsp70) and their relationship with sperm quality in varicocele (VAR) patients. Semen samples were obtained from 16 subfertile men diagnosed as VAR and 10 fertile men who applied to the Andrology Laboratory of Istanbul Medical Faculty of Istanbul University. The sperm TR and iHsp 70 expression levels were determined using Western blot analysis. The TR activity of the sperm was assayed spectrophometrically. The sperm quality was evaluated both by conventional sperm analysis and by a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) technique that assayed DNA-fragmented spermatozoa in semen samples. The percentage of TUNELopositive spermatozoa in the VAR group (16.3%±5.6%) was higher than that in the fertile group (5.5%±1.9%). Significant inverse correlations were detected between the percentage of TUNEL-positive cells and both the concentration (r=--0.609; P=0.001) and motility (r=--0.550; P=-0.004) of spermatozoa. Both the TR expression and activity were increased significantly in the VAR group (U=22.0; P=0.001 and U=33.5 P=0.012, respectively) as analyzed using the Mann-Whitney UWilcoxon rank sum Wtest. Furthermore, significant positive correlations were found between TR expression and activity (r=-0.406; P=O.040) and between TR expression and the percentage of TUNEL-positive cells (r=0.665; P=-0.001). Sperm iHsp70 expression did not differ between the VAR and fertile groups. In conclusion, increased sperm TR expression might be a defense mechanism against apoptosis in the spermatozoa of men with VAR. 展开更多
关键词 DNA damage inducible heat shock protein 70 (iHsp70) thioredoxin reductase (TR) SPERMATOZOA VARICOCELE
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Prospective Clinical Application of Thioredoxin Reductase as a Novel Diagnostic Tumor Marker 被引量:1
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作者 Suofu Ye Nong Yang +9 位作者 Weiwei Ma Yanran Fu Lin Wu Yueqin Li Lihui Liu Yi Hui Yu Qiu Siqing Mei Yan Li Huihui Zeng 《Journal of Biosciences and Medicines》 2014年第4期44-53,共10页
Background: Developing a novel, efficient biomarker for detecting malignant tumors is essential for the early diagnosis of cancers. Our aim was to assess the diagnostic value of a potential plasma tumor marker, thiore... Background: Developing a novel, efficient biomarker for detecting malignant tumors is essential for the early diagnosis of cancers. Our aim was to assess the diagnostic value of a potential plasma tumor marker, thioredoxin reductase (TR), which is expressed in many types of malignant tumor, for the non-invasive detection of cancers. Methods: The plasma activities of TR were measured in 1513 patients with common clinical diseases, 59 patients with benign tumors, and 154 patients with cancers and 586 healthy controls. The area under the ROC curve (AUC) of TR and logistic regression results of different groups were compared by sensitivity, specificity and Youden’s index. Diagnostic cut-offs and clinical reference intervals were established via ROC curve analysis. Results: The logistic regression indicated that TR activity can discriminate between cancers and benign tumors or other common diseases very well (p < 0.0001), with an area under the curve from the receiver-operator characteristics between 0.91 and 0.96. The positive critical value was 2.51 and the cancer critical value was 9.90. The diagnostic gray zone (2.51 - 9.90) may be associated with benign tumors and some common clinical diseases. Conclusions: As a novel potential marker of malignant tumors with quantitative evaluation of proliferation, TR activity detection has an excellent diagnostic potential for early-stage malignant tumors. Impact: The convenient, economical, relatively non-invasive, and reproducible detection method of TR activity makes it suitable for routine clinical practice. 展开更多
关键词 thioredoxin reductase DIAGNOSTIC Marker Cancer MALIGNANT Tumor TR Activity Abnormal HYPERPLASIA Proliferation
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A novel thioredoxin reductase inhibitor inhibits cell growth and induces apoptosis in HL-60 and K562 cells 被引量:7
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作者 Zuo-fu PENG Lin-xiang LAN +4 位作者 Fang ZHAO Jing LI Qiang TAN Han-wei YIN Hui-hui ZENG 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2008年第1期16-21,共6页
Human thioredoxin reductase (TrxR) system is associated with cancer cell growth and anti-apoptosis process. Effects of 1,2-bis(1,2-benzisoselenazolone-3(2H)-ketone)ethane (BBSKE),a novel TrxR inhibitor,were investigat... Human thioredoxin reductase (TrxR) system is associated with cancer cell growth and anti-apoptosis process. Effects of 1,2-bis(1,2-benzisoselenazolone-3(2H)-ketone)ethane (BBSKE),a novel TrxR inhibitor,were investigated on human leu-kemia cell lines HL-60 and K562. BBSKE treatment induced cell growth inhibition and apoptosis in both cell lines. Apoptosis induced by BBSKE is through Bcl-2/Bax and caspase-3 pathways. Ehrlich's ascites carcinoma-bearing mice were used to inves-tigate the anti-tumor effect of BBSKE in vivo. Tumor-bearing mice treated with BBSKE showed an increase of life span with a comparable effect to cyclophosphamide (CTX). These results suggest a potential usage of BBSKE as a therapeutic agent against non-solid tumors. 展开更多
关键词 硫氧还蛋白还原酶 细胞生长 细胞凋亡 HL-60细胞 K562细胞
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Astragalin attenuates diabetic cataracts via inhibiting aldose reductase activity in rats
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作者 Na Wang Deepika Singh Qiong Wu 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2023年第8期1186-1195,共10页
AIM:To investigate the aldose reductase(AR)inhibition capacity of astragalin(AST)against streptozoticin-induced diabetic cataracts(DCs)in rats.METHODS:Ex vivo investigations were conducted by treating the lens of a go... AIM:To investigate the aldose reductase(AR)inhibition capacity of astragalin(AST)against streptozoticin-induced diabetic cataracts(DCs)in rats.METHODS:Ex vivo investigations were conducted by treating the lens of a goat placed for 72h in artificial aqueous humor(AAH)of pH 7.8 at room temperature with cataract-causing substance(55 mmol/L of galactose)and in vivo studies were performed on rats via induction with streptozotocin.AST was administered at different dose levels and scrutinize for DC activity.RESULTS:In diabetic rats,AST improved the body weight,blood insulin,and glucose as well as the levels of galactitol in a dose-dependent way,other biochemical parameters i.e.inflammatory mediators and cytokines,and also suppress AR activity.The level of the antioxidant parameters such as superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)activity were also altered on a diabetic lens after the administration of the AST.CONCLUSION:AST protects against lens opacification to avoid cataracts and polyols formation,indicating that it could be used as a potential therapeutic agent for diabetes. 展开更多
关键词 ASTRAGALIN diabetic cataract LENS OPACIFICATION aldose reductase rats
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脓毒症患者连续性血液净化治疗前后PCT Trx-1D-Lac表达及意义
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作者 曾广志 唐海莲 +2 位作者 陈海玉 曾慧志 梅林 《河北医学》 2024年第1期50-55,共6页
目的:探讨脓毒症患者连续性血液净化(CBP)治疗前后血清降钙素原(PCT)、硫氧还蛋白-1(Trx-1)、D-乳酸(D-Lac)水平变化,分析其对CBP疗效的预测价值及临床意义。方法:选取2021年1月至2022年12月本院100例脓毒症患者作为观察组,另遵循1∶1... 目的:探讨脓毒症患者连续性血液净化(CBP)治疗前后血清降钙素原(PCT)、硫氧还蛋白-1(Trx-1)、D-乳酸(D-Lac)水平变化,分析其对CBP疗效的预测价值及临床意义。方法:选取2021年1月至2022年12月本院100例脓毒症患者作为观察组,另遵循1∶1配对原则,选取100例健康体检者作为对照组。统计两组血清PCT、Trx-1、D-Lac水平。观察组接受CBP治疗,依据治疗效果分为存活亚组、死亡亚组。比较不同亚组血清PCT、Trx-1、D-Lac水平、急性生理学与慢性健康状况Ⅱ评分(APACHEⅡ)及治疗前后其变化差值。Pearson分析各血清指标水平变化差值与APACHEⅡ评分相关性。采用受试者工作特征曲线(ROC)及曲线下面积(AUC)分析各血清指标水平变化差值对疗效的预测价值。采用卡普兰-迈耶(Kaplan-Meier)分析不同血清表达者28d内生存状况。结果:观察组血清PCT、Trx-1、D-Lac水平高于对照组(P<0.05);治疗1周后,死亡亚组血清PCT、Trx-1、D-Lac水平及APACHEⅡ评分高于存活亚组,且变化差值小于存活亚组(P<0.05);各血清指标水平变化差值与APACHEⅡ评分呈正相关(P<0.05);各血清指标水平变化差值联合预测CBP疗效的AUC分别大于单一指标预测、各血清指标联合预测(P<0.05);PCT、Trx-1、D-Lac水平变化差值高表达者死亡风险分别是低表达的4.828、3.600、2.318倍,且生存率高于低表达者(P<0.05)。结论:脓毒症患者CBP治疗前后血清PCT、Trx-1、D-Lac水平变化可反映病情严重程度,且与28d内生存情况密切相关,联合检测其变化差值对CBP疗效具有一定预测价值。 展开更多
关键词 脓毒症 连续性血液净化 降钙素原 硫氧还蛋白-1 D-乳酸
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高粱种质资源成熟期氮效率评价及筛选
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作者 李丹 曲匡正 +2 位作者 陆晓春 丛玲 朱振兴 《辽宁农业科学》 2024年第2期83-85,共3页
氮素作为影响作物生长发育的重要元素,是限制作物高产的重要限制因素之一。硝酸还原酶(Nitrate Reductase,简称NR)作为高等植物氮素吸收利用的限速酶,直接调节氮代谢。因此,叶片硝酸还原酶活性作为影响高粱产量的重要生理指标被用于评... 氮素作为影响作物生长发育的重要元素,是限制作物高产的重要限制因素之一。硝酸还原酶(Nitrate Reductase,简称NR)作为高等植物氮素吸收利用的限速酶,直接调节氮代谢。因此,叶片硝酸还原酶活性作为影响高粱产量的重要生理指标被用于评价氮素吸收、利用效率。本研究选取了97份不同来源的高粱材料,通过对97份高粱材料进行成熟期倒二叶和倒三叶的硝酸还原酶活性测定,为筛选高粱氮高效材料奠定基础。 展开更多
关键词 高粱 硝酸还原酶 筛选
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血必净注射液对心脏骤停/心肺复苏后大鼠神经功能及生存情况的影响机制
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作者 黄德庆 高玉广 +5 位作者 张元侃 王政林 邓海霞 黄夏冰 庞延 吴林 《中国药房》 CAS 北大核心 2024年第6期653-658,共6页
目的基于S-亚硝基谷胱甘肽还原酶(GSNOR)/S-亚硝基谷胱甘肽(GSNO)途径探讨血必净注射液对大鼠心脏骤停(CA)/心肺复苏(CPR)后神经功能及生存情况影响的潜在机制。方法以室颤法建立CA/CPR大鼠模型,以假手术组大鼠为参照,采用高通量测序分... 目的基于S-亚硝基谷胱甘肽还原酶(GSNOR)/S-亚硝基谷胱甘肽(GSNO)途径探讨血必净注射液对大鼠心脏骤停(CA)/心肺复苏(CPR)后神经功能及生存情况影响的潜在机制。方法以室颤法建立CA/CPR大鼠模型,以假手术组大鼠为参照,采用高通量测序分析挖掘两者差异表达基因,并结合酶联免疫吸附测定(ELISA)法检测其海马组织中GSNOR、GSNO含量;筛选血必净注射液活性成分,并与GSNOR进行分子对接。将同法造模成功的大鼠分为模型组(30只)、抑制剂(GSNOR抑制剂)组(30只)、血必净组(30只)、血必净+抑制剂组(30只),并设置假手术组(30只),分别于药物首次干预后3h、24h、3d时进行神经功能评价及生存情况记录,并检测上述时间点各组大鼠海马组织中GSNOR、GSNO含量,分析GSNOR、GSNO含量与大鼠改良的神经系统损害严重程度评分表(mNSS)评分的相关性。结果GSNOR编码基因是模型组与假手术组间的差异表达基因之一;与假手术组比较,模型组大鼠海马组织中GSNOR含量显著升高,而GSNO含量显著降低(P<0.05)。血必净注射液中去甲丹参酮、鼠尾草酚酮等活性成分与GSNOR蛋白的结合能均低于-6 kcal/mol,以氢键连接为主。动物实验结果显示,模型组大鼠各时间点的mNSS评分和海马组织中GSNOR含量均显著高于假手术组(P<0.05),生存率和GSNO含量均显著低于假手术组(P<0.05);各给药组大鼠上述指标均显著改善,且血必净组mNSS评分显著低于抑制剂组,抑制剂组GSNOR、GSNO含量的变化较血必净组更明显,血必净+抑制剂组各指标均显著优于血必净组和抑制剂组(P<0.05)。GSNOR含量与mNSS评分呈正相关,GSNO含量与mNSS评分呈负相关(P<0.05)。结论血必净注射液可以改善CA/CPR后大鼠的神经功能,提高其生存率,该作用可能与下调GSNOR并上调GSNO有关。 展开更多
关键词 血必净注射液 心脏骤停 心肺复苏 S-亚硝基谷胱甘肽 S-亚硝基谷胱甘肽还原酶
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血清成纤维细胞生长因子-21、亚甲基四氢叶酸还原酶基因多态性与妊娠期亚临床甲状腺功能减退症的相关性
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作者 赵云虹 侯临平 +1 位作者 李盛华 杨俊英 《中国医药导报》 CAS 2024年第15期88-91,共4页
目的 探究血清成纤维细胞生长因子-21(FGF-21)、亚甲基四氢叶酸还原酶(MTHFR)基因多态性与妊娠期亚临床甲状腺功能减退症(SCH)的相关性。方法 选取2022年7月至2023年7月山西省临汾市人民医院收诊的妊娠期SCH患者106例为SCH组,另选取院... 目的 探究血清成纤维细胞生长因子-21(FGF-21)、亚甲基四氢叶酸还原酶(MTHFR)基因多态性与妊娠期亚临床甲状腺功能减退症(SCH)的相关性。方法 选取2022年7月至2023年7月山西省临汾市人民医院收诊的妊娠期SCH患者106例为SCH组,另选取院内同期孕检的健康妊娠期女性106例为健康组。收集两组病历资料,筛查SCH的相关因素,分析血清FGF-21、MTHFR基因多态性对SCH发生的评估效能。结果 SCH组的空腹血糖、血清促甲状腺素(TSH)、FGF-21高于健康组(P<0.05);两组CC、CT、TT基因型分布频率比较,差异有统计学意义(P<0.05)。SCH组T等位基因分布频率高于健康组(P<0.05)。多因素分析结果显示,血清FGF-21(OR=3.330,95%CI:1.138~9.743)、MTHFR基因多态性(OR=4.104,95%CI:1.403~12.008)是SCH发生的影响因素(P<0.05)。血清FGF-21、MTHFR基因多态性单一及联合诊断SCH发生的受试者操作特征曲线下面积分别为0.738、0.670、0.851。结论 血清FGF-21水平升高、MTHFR基因TT基因型的妊娠期女性SCH发生风险更高,两项联合具有一定的诊断价值。 展开更多
关键词 亚临床甲状腺功能减退症 成纤维细胞生长因子 亚甲基四氢叶酸还原酶
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T2DM患者外周血氧化应激变化及其与合并NAFLD的关系研究
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作者 孟令华 位庚 +2 位作者 常湛 赵永晓 刘红利 《中国实验诊断学》 2024年第4期429-433,共5页
目的检测2型糖尿病(T2DM)患者外周血氧化应激变化,并分析其与合并非酒精性脂肪性肝病(NAFLD)的关系。方法选取本单位2016年1月至2017年12月收治的133例T2DM患者,随访5年,统计NAFLD发生率。根据是否发生NAFLD记为发生组(n=98)和未发生组(... 目的检测2型糖尿病(T2DM)患者外周血氧化应激变化,并分析其与合并非酒精性脂肪性肝病(NAFLD)的关系。方法选取本单位2016年1月至2017年12月收治的133例T2DM患者,随访5年,统计NAFLD发生率。根据是否发生NAFLD记为发生组(n=98)和未发生组(n=35),比较2组患者一般资料和外周血超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-PX)、硫氧还蛋白互作蛋白(TXNIP)水平;采用Logistic回归分析探讨T2DM患者并发NAFLD的危险因素;绘制受试者工作特征(ROC)曲线分析外周血SOD、MDA、GSH-PX、TXNIP水平单独与联合对T2DM患者并发NAFLD的预测价值。结果T2DM患者中NAFLD发生率为73.68%(98/133);NAFLD发生患者外周血MDA、TXNIP水平均高于NAFLD未发生患者(P<0.05),SOD、GSH-PX水平低于NAFLD未发生患者(P<0.05);病程>5年,未进行胰岛素降糖,空腹血糖,外周血SOD、MDA、GSH-PX、TXNIP水平均是T2DM并发NAFLD的影响因素(OR=3.062、3.725、4.350、0.649、4.328、0.551、4.697,P<0.05);外周血SOD、MDA、GSH-PX、TXNIP水平联合预测T2DM并发NAFLD的灵敏度均高于单独预测(P<0.01),AUC均高于单独预测(P<0.05),特异度均与单独预测差异无统计学意义(P>0.05)。结论外周血氧化应激水平升高可增加T2DM并发NAFLD的风险,外周血SOD、MDA、GSH-PX、TXNIP水平联合预测并发NAFLD的效能高。 展开更多
关键词 2型糖尿病 氧化应激 硫氧还蛋白互作蛋白 非酒精性脂肪性肝病
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MTHFR基因多态性对脑梗死患者阿替普酶静脉溶栓后出血性转化的影响
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作者 陆景红 王训 《中国现代医学杂志》 CAS 2024年第4期66-71,共6页
目的分析亚甲基四氢叶酸还原酶(MTHFR)基因多态性对脑梗死患者阿替普酶静脉溶栓后出血性转化(HT)的影响。方法回顾性分析2020年7月—2023年7月在安徽医科大学附属阜阳人民医院接受治疗的120例脑梗死患者的临床资料。依据治疗后24~72 h H... 目的分析亚甲基四氢叶酸还原酶(MTHFR)基因多态性对脑梗死患者阿替普酶静脉溶栓后出血性转化(HT)的影响。方法回顾性分析2020年7月—2023年7月在安徽医科大学附属阜阳人民医院接受治疗的120例脑梗死患者的临床资料。依据治疗后24~72 h HT发生情况分为HT组(15例)、无HT组(105例)。比较两组基线资料、MTHFR基因多态性、纤维蛋白原(Fib)、同型半胱氨酸(Hcy)。采用多因素一般Logistic回归模型分析脑梗死患者阿替普酶静脉溶栓后HT发生的危险因素。绘制受试者工作特征(ROC)曲线,分析入院时美国国立卫生院卒中量表(NIHSS)评分、Hcy预测脑梗死患者阿替普酶静脉溶栓后HT发生的价值。结果HT组心房颤动发生率、MTHFR基因型677CT占比、入院时NIHSS评分、Hcy水平均高于无HT组(P<0.05)。多因素一般Logistic回归分析结果显示:心房颤动史[OR=1.478(95%CI:1.126,1.940)]、入院时NIHSS评分升高[OR=1.656(95%CI:1.125,2.438)]、MTHFR基因型为677CT[OR=1.871/2.362(95%CI:1.052,3.328/1.081,4.652)]、Hcy水平升高[OR=2.149(95%CI:1.108,4.168)]均为脑梗死患者阿替普酶静脉溶栓后HT发生的危险因素(P<0.05)。ROC曲线分析结果显示,入院时NIHSS评分、Hcy均可预测脑梗死患者阿替普酶静脉溶栓后HT发生,其敏感性分别为80.0%(95%CI:0.765,0.883)、73.3%(95%CI:0.717,0.834),特异性分别为74.3%(95%CI:0.659,0.817)、74.3%(95%CI:0.824,0.931)。677CT型患者Hcy水平高于677CC、677TT型患者(P<0.05)。结论心房颤动、MTHFR基因型、入院时NIHSS评分、Hcy均为影响脑梗死患者阿替普酶静脉溶栓后HT发生的重要因素,临床应结合以上指标对高危患者进行重点筛查,尽早采取干预措施。 展开更多
关键词 脑梗死 基因多态性 亚甲基四氢叶酸还原酶 阿替普酶 出血性转化
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基于CRISPR/Cas12a的叶酸代谢位点MTHFR基因C677T多态性检测方法的建立
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作者 田石 安莉莎 +3 位作者 马瑶 金孝华 马旭 张璐 《生殖医学杂志》 CAS 2024年第6期785-791,共7页
目的开发一种基于CRISPR/Cas12a技术的叶酸代谢位点c.677(MTHFR C677T)的高效检测方法,以实现对C677T多态性的快速、准确分析。方法采用重组酶聚合酶扩增(RPA)结合CRISPR/Cas12a建立单管检测反应体系,建立人MTHFR基因C677T基因分型策略... 目的开发一种基于CRISPR/Cas12a技术的叶酸代谢位点c.677(MTHFR C677T)的高效检测方法,以实现对C677T多态性的快速、准确分析。方法采用重组酶聚合酶扩增(RPA)结合CRISPR/Cas12a建立单管检测反应体系,建立人MTHFR基因C677T基因分型策略;测试200例孕妇人群样本MTHFR基因C677T多态性,并与常规PCR产物测序结果进行一致率比较。结果基于CRISPR/Cas12a检测人MTHFR基因C677T多态性的检测方法结果准确、特异性好,与PCR产物测序结果具有高度一致性。结论建立的基于CRISPR/Cas12a检测技术的人MTHFR C677T基因分型方法简单、快捷、精准,为叶酸代谢位点MTHFR C677T基因型检测提供了新的途径,具有潜在的临床应用前景。 展开更多
关键词 人亚甲基四氢叶酸还原酶基因 多态性 CRISPR/Cas12a 恒温扩增
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DHCR7基因在胃癌中的表达及其与免疫相关基因的关系
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作者 王业忠 杨明华 +1 位作者 曹少锋 梅璐 《河南医学研究》 CAS 2024年第7期1153-1159,共7页
目的探究7-脱氢胆固醇还原酶(DHCR7)基因在胃癌中的表达及其与免疫相关基因的关系。方法使用UALCAN、TIMER数据库分析DHCR7基因在不同类型肿瘤中的表达情况。使用GEPIA、TCGA、GEO数据库分析DHCR7基因在胃癌中的表达。Kaplan-Meier Plot... 目的探究7-脱氢胆固醇还原酶(DHCR7)基因在胃癌中的表达及其与免疫相关基因的关系。方法使用UALCAN、TIMER数据库分析DHCR7基因在不同类型肿瘤中的表达情况。使用GEPIA、TCGA、GEO数据库分析DHCR7基因在胃癌中的表达。Kaplan-Meier Plotter数据库分析DHCR7基因表达与胃癌患者预后的相关性。通过cBioPortal数据库找出与DHCR7共表达的基因,并展示这些基因中相关系数比较高的基因。对胃癌中与DHCR7表达正负相关的基因进行基因本体分析(GO)和京都基因与基因组百科全书(KEGG)分析,首先分析DHCR7基因与CD8^(+)T细胞以及招募CD8^(+)T细胞相关趋化因子的相关性;其次分析DHCR7基因与免疫激活相关基因的相关性;最后分析DHCR7表达与胃癌患者临床病理学特征的关联。结果DHCR7基因在大多数肿瘤类型中均有高表达趋势。DHCR7基因在胃癌中的表达高于正常胃黏膜。Kaplan-Meier Plotter数据库中201790-s-at芯片结果显示高表达DHCR7组患者生存期较短。与DHCR7负相关基因的GO、KEGG通路富集分析主要富集在免疫相关功能和信号通路上,DHCR7与CD8^(+)T细胞、招募CD8^(+)T细胞相关的趋化因子以及免疫激活基因都具有负相关性。DHCR7高表达与胃癌患者年龄呈正相关。结论DHCR7在胃癌组织中呈高表达,高表达DHCR7患者预后不良,DHCR7基因能够影响胃癌免疫微环境,有望成为胃癌免疫治疗的新靶点。 展开更多
关键词 7-脱氢胆固醇还原酶 胃癌 TCGA GEO 免疫 CD8^(+)T细胞
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日本血吸虫thioredoxin基因的克隆和表达 被引量:2
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作者 邵筱 余新炳 +3 位作者 吴忠道 王海 梁柏年 李宝华 《热带医学杂志》 CAS 2004年第2期126-129,共4页
目的结合分子生物学和生物信息学方法筛选鉴定日本血吸虫新基因。方法从日本血吸虫(Schistosomajaponicum,大陆株)成虫cDNA文库中获取表达序列标签(expressedsequencetag,EST),用电子拼接的方法延伸序列,用NCBI提供的BLASTx程序和Genban... 目的结合分子生物学和生物信息学方法筛选鉴定日本血吸虫新基因。方法从日本血吸虫(Schistosomajaponicum,大陆株)成虫cDNA文库中获取表达序列标签(expressedsequencetag,EST),用电子拼接的方法延伸序列,用NCBI提供的BLASTx程序和Genbank数据库进行同源性分析以筛选基因;设计特异性引物从日本血吸虫成虫mRNA中扩增筛选基因并预测和分析;扩增产物克隆到原核表达载体并表达。结果筛选出日本血吸虫Thioredoxin全长基因并对其进行了序列分析,克隆全长cDNA至PET原核载体并表达成功。结论结合EST、电子延伸和传统的分子生物学方法是高效筛选S.japonicum功能基因的有效策略。 展开更多
关键词 日本血吸虫 thioredoxin 基因克隆 基因表达 硫氧还蛋白
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抗细菌硫氧化还原蛋白Thioredoxin单克隆抗体的制备、鉴定与初步应用 被引量:3
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作者 刘飞 刘崟 +3 位作者 金伯泉 董帮权 刘惠萍 朱勇 《细胞与分子免疫学杂志》 CAS CSCD 1999年第3期221-221,224,共2页
硫氧化还原蛋白Thioredoxin(Trx)是一类存在于细菌、植物及动物等多种生物体内的耐热蛋白[1],含有保守的WCGPC序列。还原态的Trx具有很强的蛋白二硫键氧化还原酶活性,作为核酸还原酶的供氢体在DNA的合成与复... 硫氧化还原蛋白Thioredoxin(Trx)是一类存在于细菌、植物及动物等多种生物体内的耐热蛋白[1],含有保守的WCGPC序列。还原态的Trx具有很强的蛋白二硫键氧化还原酶活性,作为核酸还原酶的供氢体在DNA的合成与复制中起重要作用。大肠杆菌Trx蛋白... 展开更多
关键词 硫氧化还原蛋白 thioredoxin 单克隆抗体 制备
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有氧运动上调硫氧还蛋白系统抑制衰老大鼠心肌细胞凋亡
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作者 徐政 赵晓琴 +5 位作者 陈肖丹 王嘉璞 鲍粉苗 于亮 李俊平 魏延 《中国组织工程研究》 CAS 北大核心 2024年第34期5508-5515,共8页
背景:研究表明,心肌细胞凋亡与心脏功能减退及心脏衰老过程密切相关,适宜的运动可以改变心力衰竭患者的心泵功能以及减轻衰老引起的心肌细胞凋亡、肥大和纤维化损伤。目的:探究长期有氧运动对衰老大鼠心肌细胞凋亡及硫氧还蛋白系统的影... 背景:研究表明,心肌细胞凋亡与心脏功能减退及心脏衰老过程密切相关,适宜的运动可以改变心力衰竭患者的心泵功能以及减轻衰老引起的心肌细胞凋亡、肥大和纤维化损伤。目的:探究长期有氧运动对衰老大鼠心肌细胞凋亡及硫氧还蛋白系统的影响。方法:选取雄性SD大鼠36只,按照鼠龄分为青年组(3月龄)、中年组(9月龄)、老年组(18月龄),每组12只;每组又分为安静、运动2个亚组,每组6只,安静组常规饲养,运动组进行有氧运动训练(45 min/d,5 d/周,训练10周)。末次训练后24 h,采用ELISA法检测大鼠血清肌钙蛋白Ⅰ和血清肌酸激酶同工酶MB水平,TUNEL染色检测心肌细胞凋亡,Western Blot检测大鼠心肌组织中Bax、Bcl-2、Caspase 3、硫氧还蛋白1、硫氧还蛋白2、硫氧还蛋白还原酶1、硫氧还蛋白还原酶2、硫氧还蛋白相互作用蛋白、凋亡信号调节激酶1、P38丝裂原活化激酶的蛋白表达。结果与结论:(1)老年安静组大鼠血清肌钙蛋白Ⅰ和肌酸激酶同工酶MB水平高于青年安静组、中年安静组、老年运动组(P <0.01),老年运动组大鼠血清肌钙蛋白Ⅰ和肌酸激酶同工酶MB水平高于青年运动组、中年运动组(P <0.01);(2)无论是安静状态还是运动训练后,随着鼠龄的增加,大鼠凋亡心肌细胞数量及Bax、Caspase 3蛋白表达逐渐升高,Bcl-2蛋白表达逐渐降低;与同龄段安静组相比,运动组大鼠凋亡心肌细胞数量及Bax、Caspase 3蛋白表达均不同程度降低,Bcl-2蛋白表达均不同程度升高;(3)老年安静组大鼠心肌硫氧还蛋白1、硫氧还蛋白2、硫氧还蛋白还原酶1、硫氧还蛋白还原酶2蛋白表达低于青年安静组、中年安静组、老年运动组(P <0.05,P <0.01);老年运动组大鼠心肌硫氧还蛋白1、硫氧还蛋白2、硫氧还蛋白还原酶2蛋白表达低于青年运动组(P <0.05,P <0.01),硫氧还蛋白还原酶1、硫氧还蛋白还原酶2蛋白表达低于中年运动组(P <0.01);(4)老年安静组大鼠心肌硫氧还蛋白相互作用蛋白、凋亡信号调节激酶1、P38丝裂原活化激酶蛋白表达高于青年安静组、中年安静组、老年运动组(P <0.01),老年运动组大鼠心肌硫氧还蛋白相互作用蛋白、凋亡信号调节激酶1、P38丝裂原活化激酶蛋白表达高于青年运动组、中年运动组(P <0.01);(5)结果表明,有氧运动可能通过下调硫氧还蛋白相互作用蛋白表达来增强硫氧还蛋白的表达,下调凋亡信号调节激酶1及P38丝裂原活化激酶蛋白的表达,从而减轻衰老大鼠心肌细胞的凋亡。 展开更多
关键词 有氧运动 衰老大鼠 心肌细胞 细胞凋亡 硫氧还蛋白
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High-throughput fluorescent screening of thioredoxin reductase inhibitors to inhibit Mycobacterium tuberculosis
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作者 Fei Yan Xin Zhao +6 位作者 Ruibo Li Xiuyan Han Qiulong Yan Lei Feng Xiulan Xin Jingnan Cui Xiaochi Ma 《Chinese Chemical Letters》 SCIE CAS CSCD 2024年第3期358-362,共5页
Tuberculosis(TB)is a chronic infectious disease,which is caused by the pathogen Mycobacterium tuberculosis(Mtb)and reemerged as a global health risk with a significant proportion of multi-drug resistant and extensivel... Tuberculosis(TB)is a chronic infectious disease,which is caused by the pathogen Mycobacterium tuberculosis(Mtb)and reemerged as a global health risk with a significant proportion of multi-drug resistant and extensively drug resistant TB cases.It is very urgent to find some novel high-confidence drug targets in Mtb for discovering the effective anti-TB agents.Thioredoxin reductase(TrxR)has been identified to be a highly viable target for anti-TB drugs for its important role in protecting the pathogen from thiol-specific oxidizing stress,regulating intracellular dithiol/disulfide homeostasis and DNA replication and repair.In the present work,a near-infrared(NIR)fluorescent probe DDAT was developed for the detection of TrxR activity and used to high-throughput screen the TrxR inhibitors from natural products.Two screened TrxR inhibitors from Sappan Lignum and microbial metabolites that were further used to inhibit Mycobacterium tuberculosis.All the results indicate that DDAT is a practical fluorescent molecular tool for the discovery of potential anti-TB drugs. 展开更多
关键词 thioredoxin reductase NIR fluorescent probe Fluorescence imaging High-throughput screening inhibitors Inhibit Mycobacterium tuberculosis
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多枝赖草Glutathione Reductase基因克隆及胁迫表达分析 被引量:6
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作者 史仁玖 郝岗平 +1 位作者 赵茂林 杨清 《四川师范大学学报(自然科学版)》 CAS CSCD 北大核心 2008年第4期471-475,共5页
为了获得完整的谷胱甘肽还原酶基因序列,根据已克隆到的谷胱甘肽还原酶cDNA片段设计引物,利用RACE扩增获得了基因全长序列,应用Southern印迹杂交法分析基因存在状态,Northern印迹杂交法研究基因表达情况.结果表明,该基因全长1580 bp,含... 为了获得完整的谷胱甘肽还原酶基因序列,根据已克隆到的谷胱甘肽还原酶cDNA片段设计引物,利用RACE扩增获得了基因全长序列,应用Southern印迹杂交法分析基因存在状态,Northern印迹杂交法研究基因表达情况.结果表明,该基因全长1580 bp,含一个1 140 bp的开放阅读框架,编码380个氨基酸,与其它植物谷胱甘肽还原酶氨基酸序列的同源性在77%-92%之间;Southern杂交表明该基因有一个拷贝;Northern杂交表明在逆境胁迫下GR基因表达加强. 展开更多
关键词 多枝赖草 谷胱甘肽还原酶 盐胁迫 表达
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