Aldo-keto reductase family member C3(AKR1C3)promotes hepatocellular carcinoma cell growth by producing prostaglandin F2α

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.

Astragalin attenuates diabetic cataracts via inhibiting aldose reductase activity in rats

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.

Relationship between granulomatous lobular mastitis and methylene tetrahydrofolate reductase gene polymorphism

BACKGROUND Variations in the methylene tetrahydrofolate reductase(MTHFR)gene have been reported as risk factors for numerous conditions,including cardiovascular disease,thrombophilia,stroke,hypertension and pregnancy-related complications.Moreover,it was reported there is an association between breast cancer and mutations in MTHFR-C677T.However,whether there is an association between MTHFR gene polymorphism and granulomatous lobular mastitis or not has been rarely investigated.AIM To analyze the association between MTHFR gene polymorphism and granulomatous lobular mastitis.METHODS Fifty-one patients with granulomatous lobular mastitis admitted to The First Hospital of Kunming were selected as study samples.Their hospitalization time ranged from February 2018 to February 2019.The 51 patients were included in the experimental group,and another 51 women who underwent physical examination at The First Hospital of Kunming in the same period were included in the control group.Deoxyribonucleic acid and MTFR genetic polymorphism testing were performed in each group.The association between MTHFR gene polymorphism and granulomatous lobular mastitis was observed.RESULTS There were significant differences in genotype frequency and allele frequency of C/C and C/T between the experimental group and the control group(all P<0.05).However,there was no significant difference in frequency of T/T genotype between the two groups(P>0.05).In addition,there was no significant difference in genotype frequency and allele frequency of A/A,A/C and C/C between the two groups(P>0.05).CONCLUSION MTHFR gene C677T locus polymorphism is closely related to granulomatous lobular mastitis.

Eff ects of temperature on photosynthetic performance and nitrate reductase activity in vivo assay in Gracilariopsis lemaneiformis (Rhodophyta)

Gracilariopsis lemaneiformis is an economically-valued species and widely cultured in China at present.After being acclimated to diff erent growth temperatures(15,20,25,and 30°C)for 7 days,the relative growth rate(RGR),nitrate reductase activity,soluble protein content and chlorophyll a fl uorescence of G.lemaneiformis were examined.Results show that RGR was markedly aff ected by temperature especially at 20°C at which G.lemaneiformis exhibited the highest eff ective quantum yield of PSII[Y(II)]and lightsaturated electron transport rate(ETR max),but the lowest non-photochemical quenching.Irrespective of growth temperature,the nitrate reductase activity increased with the incubation temperature from 15 to 30°C.In addition,the greatest nitrate reductase activity was found in the thalli grown at 20°C.The value of temperature coeffi cient Q10 of alga cultured in 15°C was the greatest among those of other temperatures tested.Results indicate that the optimum temperature for nitrate reductase synthesis was relatively lower than that for nitrate reductase activity,and the relationship among growth,photosynthesis,and nitrate reductase activity showed that the optimum temperature for activity of nitrate reductase in vivo assay should be the same to the optimal growth temperature.

固相萃取-高效液相色谱法检测食品中酸性大红GR

建立了高效液相色谱法测定多种食品中非法染料酸性大红GR的分析方法,并对样品的提取溶剂、净化方式及色谱条件进行了优化。样品采用1%氨化甲醇溶液提取,PWAX萃取柱净化浓缩,以10 mmol乙酸铵-甲醇为流动相,经Titank C18色谱柱分离,采用二极管阵列检测器测定。结果显示,酸性大红GR在0.040〜10.00μg/mL线性关系良好(R2>0.999),检出限和定量限分别为0.025和0.10 mg/kg。在阴性样品中添加0.10、0.20、1.00 mg/kg三水平加标,平均回收率为80.14%〜102.60%,相对标准偏差为1.08%〜4.29%。通过与食品补充检验方法比较,验证了本方法测定辣椒制品、水产制品和饮料中酸性大红GR的准确性,同时对其他食品中酸性大红GR进行测定,结果证明该方法灵敏度高、回收率好,为食品安全的监管提供了技术支持。

Feedback regulation of cholesterol synthesis： sterol-accelerated ubiquitination and degradation of HMG CoA reductase

3-hydroxy-3-methylglutaryl 辅酶 a (HMG CoA ) reductase 生产 mevalonate，在胆固醇和必需品的合成的重要中介非甾醇 isoprenoids。reductase 通过被甾醇并且非调停的多重机制服从于反馈控制的过高的数量 mevalonate 的甾醇结束产品新陈代谢。这里，我将讨论为 reductase 的控制使一机制清楚些的最近的进展，它包含酶的快速的降级。某些甾醇的累积触发 reductase 的绑定到 endoplasmic (嗯) 膜蛋白质叫了 Insig-1 和 Insig-2。在联系膜的 ubiquitin 连接酶的招募的 Reductase-Insig 有约束力的结果叫了 gp78，它开始 reductase 的 ubiquitination。这 ubiquitination 是为 reductase 从的识别和降级的应尽的反应嗯由 cytosolic 26S proteasomes 的膜。因此， reductase 的加速甾醇的降级代表一般细胞的进程(嗯联系降级) 怎么被用来控制一条重要新陈代谢的小径(胆固醇合成) 的一个例子。

Fabrication of Graphene/Cu Composite by Chemical Vapor Deposition and Effects of Graphene Layers on Resultant Electrical Conductivity

Graphene(Gr)has unique properties including high electrical conductivity;Thus,graphene/copper(Gr/Cu)composites have attracted increasing attention to replace traditional Cu for electrical applications. However,the problem of how to control graphene to form desired Gr/Cu composite is not well solved. This paper aims at exploring the best parameters for preparing graphene with different layers on Cu foil by chemical vapor deposition(CVD)method and studying the effects of different layers graphene on Gr/Cu composite’s electrical conductivity. Graphene grown on single-sided and double-sided copper was prepared for Gr/Cu and Gr/Cu/Gr composites. The resultant electrical conductivity of Gr/Cu composites increased with decreasing graphene layers and increasing graphene volume fraction. The Gr/Cu/Gr composite with monolayer graphene owns volume fraction of less than 0.002%,producing the best electrical conductivity up to59.8 ×10^(6)S/m,equivalent to 104.5% IACS and 105.3% pure Cu foil.

GR 125487加剧帕金森病模型小鼠运动障碍和促进肠道炎症的研究

目的探究5-羟色胺受体在帕金森病模型小鼠肠道表达及5-羟色胺4受体对帕金森病模型小鼠运动功能、神经递质及肠道炎症的作用。方法通过RT-qPCR方法检测帕金森病模型小鼠回肠、结肠的5-羟色胺受体mRNA表达水平(Htr1a,Htr1b,Htr1f,Htr2a,Htr2c,Htr4,Htr6和Htr7);将C57BL/6N小鼠随机分成生理盐水组(saline组)、模型组(MPTP组)、5-羟色胺4受体拮抗剂+MPTP组(GR 125487+MPTP组)3组。在第1~5 d连续5 d腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine,MPTP)建立小鼠帕金森病模型。连续16 d每天腹腔注射5-羟色胺4受体拮抗剂GR 125487以探究5-羟色胺4受体对帕金森病模型小鼠的作用。最后一天给药后进行小鼠行为学测试,测试完成后收集小鼠纹状体及结肠组织。通过高效液相色谱法检测纹状体内多巴胺(dopamine,DA)及其代谢物含量,通过Western blot方法检测结肠内CD11b的蛋白表达水平。结果RT-qPCR结果显示,与Saline组相比,MPTP组小鼠回肠、结肠Htr4显著升高(P<0.05)。行为学结果显示,MPTP组小鼠运动能力显著下降(P<0.01),而GR 125487+MPTP组小鼠运动障碍加剧(P<0.05);HPLC结果显示,MPTP组纹状体DA显著减少,DA代谢率显著升高,而GR 125487+MPTP组小鼠进一步减少脑内DA水平,增加DA代谢率;Western blot结果显示,CD11b在GR 125487+MPTP组小鼠结肠表达水平相比于MPTP组表达水平显著上升(P<0.05)。结论Htr4在MPTP诱导的帕金森病模型小鼠肠道表达异常,5-HT4受体拮抗剂可以加剧帕金森病模型小鼠运动障碍、神经递质丢失并促进肠道炎症。

A novel thioredoxin reductase inhibitor inhibits cell growth and induces apoptosis in HL-60 and K562 cells

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.

插值算子和Gröbner-Shirshov基

在一个范畴中,自由对象是非常重要的,其可以通过Gröbner-Shirshov基的方法去构造.证明在算子代数的框架下,插值算子等式是一个Gröbner-Shirshov基,作为应用,构造了自由的插值代数.

SB-265 Gr.12钛镍钼合金焊接工艺研究

介绍了SB-265 Gr.12钛镍钼合金的化学成分与力学性能,对化学成分中各元素的作用进行了阐述,并对SB-265 Gr.12钛镍钼合金的焊接性以及焊接注意事项进行了介绍。工艺评定试验采用24 mm厚的SB-265 Gr.12板材,焊接采用钨极惰性气体保护焊(GTAW)焊接方法。焊接工艺评定试板经渗透检测(PT)、射线检测(RT)检测合格后,进行拉伸、弯曲、硬度等理化试验,试验结果满足标准及相关工程规范的要求。对焊接接头进行宏观金相及显微组织试验,宏观金相试验结果良好,母材的显微组织为α相+少量β相,基体上弥散分布着Ni_(2)Ti相,焊接热影响区的显微组织为α相+少量β相+Ni_(2)Ti相+片层状α’相,焊缝的显微组织为片层状的α’相+少量β相。

核电站SA738Gr.B主蒸汽管道贯穿件制作焊接技术

针对核电站SA738Gr.B材料进行焊接性分析,通过焊材选型,制订合适的焊接工艺,并在施工中从焊接工艺规程、人员资格、作业环境、设备机具、焊前检查、焊前预热、焊接顺序、焊后消氢及消应力热处理等方面采取了有效的过程管理,使贯穿件最终无损检测合格,整体尺寸误差在允许偏差范围内,保证了产品质量,缩短了施工工期。

联合检测GR、NO、IL-6对儿童病毒性心肌炎的评价

目的联合几项免疫介导的血清学指标来提高对儿童儿童病毒性心肌炎(VMC)的诊断效率,为临床提供早期的诊断价值,避免漏检对患儿引起的不良结局。方法收集泗洪医院2018年1月至2022年6月在儿科住院就诊符合条件的45例VMC病例纳入VMC组,45例单纯病毒感染患儿纳入NVMC组以及体检的50名正常儿童纳入对照组。收集研究对象一般资料,包括白细胞介素6(IL-6)、谷胱甘肽还原酶(GR)、一氧化氮(NO)以及心肌酶谱、肌钙蛋白结果。用受试者工作特征(ROC)曲线各单项指标对VMC的价值分析,并采用Logistic回归模型构建模型来预判VMC。结果VMC组的肌酸激酶同工酶(CK-MB)、天门冬氨酸氨基转移酶(AST)、乳酸脱氢酶(LDH)、肌钙蛋白I(cTnI)、NO、IL-6含量明显高于NVMC组和对照组,而GR含量则明显低于后两组;用各单项指标来对VMC进行ROC曲线分析,结果显示特异性最高的是cTnI的0.907,敏感性最高的是IL-6的0.912,AUC面积最大的是NO,为0.883;由cTnI、CK-MB、GR、NO、IL-6等5项指标联合建立的回归模型,当诊断界值定为0.55时,模型对VMC的AUC为0.976,敏感性为0.977,特异性为0.982,此时约登指数最大为0.959。结论用NO、GR、IL-6联合cTnI、CK-MB构建的回归模型对VMC的诊断特异性以及敏感性明显高于其他的单一指标。能够为临床医生及早的诊断儿童VMC提供有力的依据和辅助。

一体模钢锭轧制特厚SA387Gr11CL2钢板生产实践

以33.2 t一体模钢锭轧制的(120×1 720×13 570) mm规格SA387Gr11CL2钢板为对象,重点研究帽口端表面、内部质量、化学成分及力学性能。结果表明:轧制钢板帽口对应位置的表面质量良好,探伤结果达到NB/T 47013.3—2015标准及第1号修改单TⅠ级。距帽口线700 mm以内试样成分无明显偏析,满足标准要求,拉伸、冲击等力学性能良好。与传统钢锭相比,采用一体模钢锭轧制上述规格钢板,成材率可以提高3.29%。

多枝赖草Glutathione Reductase基因克隆及胁迫表达分析

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.

油菜素内酯合成酶(Steroid 5α-Reductase)基因的超量表达对毛白杨生长的影响

将棉花Steroid 5α-reductase基因(DET2)超量表达载体导入毛白杨中,观察其对毛白杨生长和芽休眠的影响。结果表明,超量表达DET2基因的毛白杨茎高度、直径生长和不定根的生长增强,芽的休眠破除提前。

鼠李糖乳杆菌GR-1缓解大肠杆菌诱导的奶牛子宫内膜上皮细胞炎性反应

为明确鼠李糖乳杆菌GR-1(L.rhamnosus GR-1)在大肠杆菌感染原代奶牛子宫内膜上皮细胞(BEECs)过程中调节炎性反应的机制,本试验将BEECs分为4个组,分别是对照组(加入5 mL培养基)、E.coli攻菌组(加入5 mL浓度为1×10^(5)CFU/mL大肠杆菌)、L.rhamnosus GR-1单独处理组(提前3 h加入5 mL浓度为1×10^(7)CFU/mL L.rhamnosus GR-1)和L.rhamnosus GR-1保护组(加入5 mL浓度为1×10^(7)CFU/mL L.rhamnosus GR-1孵育3 h后去掉上清液,再加入5 mL浓度为1×10^(5)CFU/mL大肠杆菌);采用光学显微镜观察E.coli对BEECs形态的损害情况,实时荧光定量PCR检测相关基因的转录水平,Western blot检测TLR2和NF-κB2的蛋白表达。结果显示,E.coli攻菌6 h后,与E.coli攻菌组相比,L.rhamnosus GR-1保护组BEECs形态保持完整,且TLR2、TLR4、TNF-αmRNA表达量极显著下调(P<0.01或P<0.001),TLR2和NF-κB2的蛋白水平也极显著下降(P<0.001)。结果表明,L.rhamnosus GR-1可能通过TLRs下调BEECs的炎性因子表达,从而缓解E.coli感染造成的奶牛子宫内膜上皮细胞损伤,为奶牛子宫内膜炎的防治提供数据参考。

Single nucleotide polymorphism C677T in the methylenetetrahydrofolate reductase gene might be a genetic risk factor for infertility for Chinese men with azoospermia or severe oligozoospermia

Aim： To analyze the distribution of the single nucleotide polymorphism （SNP） C677T in the methylenetetrahydrofolate reductase （MTHFR） gene in 355 infertile Chinese patients with idiopathic azoospermia or severe oligozoospermia and 252 fertile Chinese men as controls to explore the possible association of the SNP and male infertility. Methods： Using the polymerase chain reaction （PCR）-restriction fragment length polymorphism technique, the allele and genotype distribution of SNP C677T in the MTHFR gene were investigated in both patients and controls. Results： The frequencies of allele T （40.9% vs 30.4%, P = 0.002, odds ration [OR] = 1.58, 95% confidence interval [CI]： 1.24-2.02） and mutant homozygote （TT） （18.3% vs. 11.5%, P = 0.023, OR = 1.72, 95% CI： 1.07-2.76） as well as carrier with allele （TT ＋ CT） （63.4% vs. 49.2%, P = 0.0005, OR = 1.79, 95% CI： 1.29-2.48） in infertile patients were significantly higher than those in controls. After patient stratification, the significant differences in distribution of the SNP between each patient subgroup and control group still remained. Conclusion： Our findings indicate that there is an association of SNP C677T in the MTHFR gene with male infertility, suggesting that this polymorphism might be a genetic risk factor for male infertility in Chinese men.

Influences of Mo on Nitrate Reductase, Glutamine Synthetase and Nitrogen Accumulation and Utilization in Mo-Efficient and Mo-Inefficient Winter Wheat Cultivars

The objective is to study whether the accumulation and utilization of plant N are controlled by Mo status in winter wheat cultivars. Mo-efficient cultivar 97003 （eft） and Mo-inefficient cultivar 97014 （ineff） were grown in severely Mo-deficient acidic soil （Tamm-reagent-extractable Mo 0.112 mg kg^-1） with （＋Mo） and without （-Mo） the application of 0.13 mg kg^-1 Mo. The accumulation and use efficiency of plant total N were significantly higher in ＋Mo than that in -Mo and in eft than that in ineff under Mo deficiency. N use efficiency was remarkably higher in maturity but it was forwarded to jointing stage after Mo supply, thus indicating that Mo supply promoted the N use efficiency besides N uptake and eff was efficient in N uptake and utilization. The overall activity of nitrate reductase （NR, EC 1.6.6.1） was significantly higher in ＋Mo than in -Mo and ratio of ＋Mo/-Mo was even to 14.8 at filleting stage for ineff. Activity of glutamine synthetase （GS, EC 6.3.1.2） was significantly lower in ＋Mo than in -Mo. Concentration of nitrate and glutamate were also significantly lower in ＋Mo than in -Mo, thus provided evidences for enhancing N use efficiency by Mo supply. Activities of NR and GS were significantly higher and concentrations of nitrate and glutamate were significantly lower in eff than ineff under Mo deficiency, thus indicated eff was more efficient in N reduction and utilization. It is therefore concluded that Mo could promote N accumulation and utilization in winter wheat which was directly related to NR and feedback regulated by GS. Higher Mo status also results in higher accumulation and utilization of plant N in eft.

Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer susceptibility

AIM: To identify the association between methylenetetrahydrofolate reductase(MTHFR) polymorphisms and gastric cancer(GC) susceptibility.METHODS: Systematic searches were performed on the electronic databases PubMed, ISI, Web of knowledge, CNKI and Wanfang, as well as manual searching of the references of the identified articles. A total of 26 papers were included in this meta-analysis. Overall and subgroup analyses were performed. Odds ratio(OR) and 95%CI were used to evaluate the associations between MTHFR polymorphisms and GC risk. The I2 statistics were used to evaluate between-study heterogeneity. Sensitivity analysis was also performed.RESULTS: Increased risk was found for the MTHFRC677T polymorphism under four genetic models(TT + CT vs CC: OR = 1.23, P = 0.002; T vs C: OR = 1.15, P = 0.001; TT vs CC: OR = 1.37, P = 0.0005; TT vs CT + CC: OR = 1.17, P = 0.0008). Subgroup analysis by ethnicity suggested that C677 T polymorphism conferred a risk of GC in eastern but not in western populations. Stratification by tumor site showed an association between the C677 T polymorphism and gastric cardia cancer and non-cardia GC in the worldwide population and in eastern populations. Regardless of comparisons with controls or diffuse-type GC, a positive association was found for the C677 T polymorphism and an increased risk of intestinal-type GC in the whole population and in western populations. With regard to the A1298 C polymorphism, we found that genotype CC was significantly decreased and conferred protection against GC in eastern populations(CC vs AA: OR = 0.44, P = 0.03; CC vs AC + AA: OR = 0.46, P = 0.04). CONCLUSION: MTHFR C677 T polymorphism is a risk factor for GC, and the A1298 C polymorphism may be a protective factor against GC in eastern populations.