Hepcidin and HFE protein: Iron metabolism as a target for the anemia of chronic kidney disease?

The anemia of chronic kidney disease and hemodialysis is characterized by chronic inflammation and release of cytokines,resulting in the upregulation of the iron hormone hepcidin,also increased by iron therapy and reduced glomerular filtration,with consequent reduction in iron absorption,recycling,and availability to the erythron.This response proves advantageous in the short-term to restrain iron availability to pathogens,but ultimately leads to severe anemia,and impairs the response to erythropoietin(Epo)and iron.Homozygosity for the common C282Y and H63D HFE polymorphisms influence iron metabolism by hampering hepcidin release by hepatocytes in response to increased iron stores,thereby resulting in inadequate inhibition of the activity of Ferroportin-1,inappropriately high iron absorption and recycling,and iron overload.However,in hemodialysis patients,carriage of HFE mutations may confer an adaptive benefit by decreasing hepcidin release in response to iron infusion and inflammation,thereby improving iron availability to erythropoiesis,anemia control,the response to Epo,and possibly survival.Therefore,anti-hepcidin therapies may improve anemia management in hemodialysis.However,HFE mutations directly favor hemoglobinization independently of hepcidin,and reduce macrophages activation in response to inflammation,whereas hepcidin might also play a beneficial anti-inflammatory and anti-microbic action during sepsis,so that direct inhibition of HFEmediated regulation of iron metabolism may represent a valuable alternative therapeutic target.Genetic studies may offer a valuable tool to test these hypotheses and guide the research of new therapies.

Evaluation of the Dietary Reference Intakes for Japanese (2010 Edition): Recommended Protein, Pantothenic acid, Vitamin D, and Iron Intakes for Breast-Fed Infants Aged 6 - 11 Months

Objective: With regard to the 2010 edition of Dietary Reference Intakes for Japanese (DRIs-2010), we investigated whether the DRIs for two age groups, breast-fed infants aged 6-8 and 9-11 months, can be fulfilled for every nutrient in actual dietary practice. Design: We evaluated (1) whether the DRIs for all nutrients can be fulfilled in a formula with energy and protein exceeding their DRIs, (2) whether the DRIs for all nutrients can be fulfilled in a formula prepared in accordance with Japanese government-recommended weaning guidelines, and (3) what kinds of formulas can be prepared if the DRIs for all nutrients are fulfilled without referring to the weaning guidelines. Setting: Simulation of diet menu on the basis of published data in our university and survey of diet menu in a university hospital attached to a national medical school. Subjects: The three types of formulas were planned for ten days. Results: It was impossible to simultaneously fulfil the DRIs for 6 - 8-month-old infants concerning pantothenic acid, vitamin D, and iron and those for 9 - 11-month-old infants concerning these nutrients plus protein. Conclusion: According to the DRIs-2010, the DRI for all nutrients could not be fulfilled in an ingestible formula.

NDUFS6蛋白生物信息学分析及过表达质粒的构建与鉴定

目的 应用生物信息学方法分析线粒体呼吸链复合体Ⅰ结构亚基烟酰胺腺嘌呤二核苷酸脱氢酶(泛素)铁硫蛋白6(NDUFS6)的理化性质,构建pCV702-NDUFS6过表达质粒并进行鉴定,为进一步研究NDUFS6蛋白功能奠定基础。方法 利用Expasy、UniProtKB、NCBI、SOPMA等生物信息学工具分析NDUFS6蛋白的理化性质、二级结构等;根据NDUFS6 cDNA序列构建携带NDUFS6基因的过表达质粒pCV702-NDUFS6,转染大鼠心肌细胞H9C2,并设置阴性对照(NC)组和相应空载体CON520作为阳性对照(PC)组,经嘌呤霉素筛选后,采用RT-qPCR和Western blot检测NDUFS6 mRNA和蛋白表达水平。结果 NDUFS6蛋白由116个氨基酸组成,理论等电点pI为9.37。蛋白二级结构以无规则卷曲(占50%)为主。酶切鉴定和基因测序结果显示,pCV702-NDUFS6表达质粒构建成功。RT-qPCR和Western blot结果显示,相较于NC组和PC组,过表达组NDUFS6表达水平均上调(P均<0.05)。结论 成功构建了能在心肌细胞H9C2中有效过表达NDUFS6基因的过表达质粒。

巨噬细胞中Piezo1调控铁代谢在年龄相关骨量丢失中的研究

目的对Piezo1蛋白在巨噬细胞参与铁代谢平衡调控中作用作一综述,总结近年来关于年龄相关骨量丢失及巨噬细胞Piezo1的最新研究进展,为治疗年龄相关骨量丢失提供新思路。方法计算机检索CNKI、PubMed等数据库自建库至2023年1月与巨噬细胞Piezo1在年龄相关骨量丢失的相关文献,中文检索关键词为“巨噬细胞、机械敏感性离子通道蛋白、年龄相关骨量丢失、骨质疏松症”,英文检索关键词为“Macrophages、Piezo1、age⁃related bone loss、ARBL、Osteoporosis”,最终将42篇文献纳入。结果与结论巨噬细胞参与铁代谢平衡的调控,骨髓巨噬细胞中Piezo1高表达能导致机体出现铁超载,进而导致ARBL的发生。Piezo1为治疗年龄相关骨量丢失提供了分子层面的新思路和新视角。

蛋白琥珀酸铁治疗重度贫血的效果观察

目的分析蛋白琥珀酸铁治疗重度贫血患者的临床疗效。方法选择700例重度贫血患者作为本次观察对象,依据治疗药物的不同分为对照组和观察组,每组350例。对照组接受多糖铁复合物治疗,观察组采用蛋白琥珀酸铁治疗。比较两组患者治疗前后的血液学指标[红细胞计数(RBC)、血红蛋白(Hb)、平均红细胞体积(MCV)、平均红细胞血红蛋白含量(MCH)]、铁代谢指标[血清铁(SI)、铁蛋白(SF)和总铁结合力(TIBC)]水平及临床疗效、不良反应发生情况。结果对照组治疗前RBC、Hb、MCV、MCH、SI、SF、TIBC分别为(2.18±0.25)×10^(12)/L、(82.65±7.82)g/L、(67.45±4.47)fl、(21.23±2.35)pg、(6.35±1.12)μmol/L、(5.68±1.29)μg/L、(80.45±8.72)μmol/L,治疗后分别为(3.69±0.32)×10^(12)/L、(123.45±8.91)g/L、(73.61±4.82)fl、(24.57±2.80)pg、(16.37±1.72)μmol/L、(62.08±6.52)μg/L、(68.54±7.25)μmol/L;观察组治疗前RBC、Hb、MCV、MCH、SI、SF、TIBC分别为(2.15±0.31)×10^(12)/L、(82.57±7.93)g/L、(67.38±4.52)fl、(21.20±2.37)pg、(6.30±1.15)μmol/L、(5.62±1.34)μg/L、(80.56±8.81)μmol/L,治疗后分别为(5.34±0.48)×10^(12)/L、(129.58±9.74)g/L、(84.92±5.13)fl、(27.62±3.01)pg、(22.04±2.25)μmol/L、(80.76±7.98)μg/L、(61.89±6.43)μmol/L;治疗前,两组RBC、Hb、MCV、MCH、SI、SF、TIBC水平比较差异无统计学意义(P>0.05)。治疗后,两组患者的RBC、Hb、MCV、MCH、SI和SF均较治疗前升高,且观察组高于对照组;TIBC较治疗前降低,且观察组低于对照组,差异有统计学意义(P<0.05)。观察组患者治疗总有效率98.57%与对照组的98.86%比较,差异无统计学意义(P>0.05)。对照组患者的不良反应发生率1.71%与观察组的2.00%比较,差异无统计学意义(P>0.05)。结论针对重度贫血患者的治疗,采用蛋白琥珀酸铁治疗具有确切的临床疗效,可有效改善患者的铁代谢功能以及血液学指标浓度,同时具有较高的用药安全性。

ADHD患儿补铁疗法的有效性研究

目的 探究补充铁剂对儿童注意缺陷多动障碍(ADHD)的疗效,为临床和家庭干预提供参考依据。方法 本研究初步纳入郑州大学附属儿童医院儿童保健科150例ADHD患儿,其中有72.4%的患儿血清铁蛋白水平低于30 ng·mL^(-1)。最终,纳入铁缺乏的患儿109例,其中男性比例为78.9%。研究采用间歇补铁法,口服蛋白琥珀酸铁,剂量为4 mg·kg^(-1)·w^(-2),疗程为12 w。期间对患儿的症状进行评估,采用Conners家长评分量表(CPRS)、ADHD评定量表(ADHD RS)评估患儿在注意力、行为和学业等方面的表现。结果 铁剂补充后,患儿的血清铁蛋白水平明显提高,注意力和行为等方面也有了改善。具体来说,铁剂补充组的患儿注意力缺陷、多动冲动症状明显减轻,但学业问题改善不显著。结论 铁缺乏症被认为是ADHD的潜在危险因素,本研究的结果则证实了铁剂补充在改善ADHD症状的治疗上具有可行性。

SMAD4过表达干预骨质疏松大鼠铁代谢相关蛋白的表达

背景:SMAD家族成员4(SMAD4)能够促进骨质疏松大鼠骨重建,然而SMAD4是否干预骨质疏松大鼠铁代谢相关蛋白表达尚不清楚。目的:探究SMAD4过表达对骨质疏松大鼠铁代谢相关蛋白表达的影响。方法:大鼠随机分为假手术组、卵巢摘除组、转染对照组和SMAD4过表达组,后3组切除卵巢建立骨质疏松大鼠模型,假手术组仅切除脂肪组织。1周后行股骨髓腔腺病毒注射,SMAD4过表达组和转染对照组分别注射过表达SMAD4基因的腺病毒及对照空载病毒,注射1个月后进行指标检测。显微CT、苏木精-伊红染色、抗酒石酸酸性磷酸酶染色检测骨质疏松大鼠骨形成和骨吸收情况;ELISA检测血清铁蛋白、铁调素水平;免疫组化染色检测股骨组织碱性磷酸酶、骨钙素、核因子κB受体激活因子配体、抗酒石酸酸性磷酸酶水平;RT-qPCR检测股骨组织SMAD4、铁调素、二价金属离子转运体1、转铁蛋白受体1、膜铁转运蛋白1 mRNA水平;Western blot检测股骨组织SMAD4、碱性磷酸酶、骨钙素、骨保护素、核因子κB受体激活因子配体、抗酒石酸酸性磷酸酶、β-胶原降解产物、铁调素、二价金属离子转运体1、转铁蛋白受体1、膜铁转运蛋白1蛋白水平。结果与结论:①假手术组大鼠股骨组织骨小梁完整,几乎未见破骨细胞;卵巢摘除组、转染对照组骨小梁稀疏,存在大量破骨细胞;SMAD4过表达组大鼠骨小梁增多,破骨细胞减少;②与假手术组相比,卵巢摘除组大鼠股骨组织SMAD4、碱性磷酸酶、骨钙素、骨保护素蛋白水平、血清和股骨组织铁调素水平明显降低,股骨组织核因子κB受体激活因子配体、抗酒石酸酸性磷酸酶、β-胶原降解产物蛋白水平、二价金属离子转运体1、转铁蛋白受体1、膜铁转运蛋白1 mRNA和蛋白水平明显升高(P<0.05);③与转染对照组相比,SMAD4过表达组大鼠股骨组织SMAD4、碱性磷酸酶、骨钙素、骨保护素蛋白水平、血清和股骨组织铁调素水平明显升高,股骨组织核因子κB受体激活因子配体、抗酒石酸酸性磷酸酶、β-胶原降解产物蛋白水平、二价金属离子转运体1、转铁蛋白受体1、膜铁转运蛋白1 mRNA和蛋白水平明显降低(P<0.05);④提示过表达SMAD4通过干预铁代谢相关蛋白表达促进骨质疏松大鼠骨重建。

蛋白琥珀酸铁联合复合维生素对缺铁性贫血孕妇红细胞参数及铁代谢的影响

目的探讨蛋白琥珀酸铁联合复合维生素对缺铁性贫血(Iron Deficiency Anemia,IDA)孕妇红细胞参数及铁代谢的影响。方法选取2021年1月—2022年10月成武县人民医院产科收治的58例IDA孕妇为研究对象,按随机数表法分为两组,各29例。对照组孕妇予以复合维生素治疗,观察组孕妇于此基础上加用蛋白琥珀酸铁口服溶液治疗。对比两组孕妇的临床疗效、红细胞参数、铁代谢指标、不良反应。结果观察组治疗总有效率为93.10%,明显高于对照组的72.41%,差异有统计学意义(χ^(2)=4.350,P<0.05)。治疗后,观察组各项红细胞参数、铁代谢指标水平均高于对照组,差异有统计学意义(P均<0.05)。观察组不良反应发生率与对照组相当,差异无统计学意义(P>0.05)。结论采用蛋白琥珀酸铁联合复合维生素治疗效果显著,可促进红细胞参数及铁代谢指标改善,且安全性高。

血清铁调节蛋白2、诱饵受体3水平与老年慢性阻塞性肺疾病急性加重期患者疾病转归的关系研究

目的探讨血清铁调节蛋白2(iron-regulated protein 2,IRP2)、诱饵受体3(decoy receptor 3,DcR3)水平与老年慢性阻塞性肺疾病急性加重期(acute exacerbation of chronic obstructive pulmonary disease,AECOPD)患者疾病转归的关系。方法选择AECOPD患者(AECOPD组)88例,检测血清IRP2、DcR3水平,追踪AECOPD患者临床疾病转归,根据临床疾病转归将其分为恶化组(22例)和好转组(66例)。多因素Logistic回归分析AECOPD患者疾病转归的影响因素。受试者工作特征曲线(receiver operating characteristic curve,ROC)分析IRP2、DcR3预测AECOPD患者疾病转归的价值。结果恶化组近1年AECOPD发作次数、急性生理和慢性健康状况评分、合并休克、呼吸困难评分(modified medical research council,mMRC)分级3~4级高于好转组(P<0.05)。恶化组治疗前和治疗2周后血清IRP2、DcR3水平高于好转组,治疗2周后好转组血清IRP2、DcR3水平低于治疗前(P<0.05);恶化组血清IRP2、DcR3水平与治疗前比较差异无统计学意义(P>0.05)。多因素Logistic回归分析结果显示,近1年AECOPD发作次数、mMRC分级、治疗前IRP2、治疗前DcR3是AECOPD患者疾病恶化的危险因素(P<0.05)。治疗前IRP2、DcR3预测AECOPD患者疾病转归的曲线下面积为0.781、0.795,联合IRP2、DcR3预测AECOPD患者疾病转归的曲线下面积为0.918,大于单独IRP2、DcR3预测(P<0.05)。结论AECOPD患者血清IRP2、DcR3水平均显著增高,且与肺功能降低以及疾病恶化有关,检测血清IRP2、DcR3水平有助于对AECOPD患者疾病转归的预测。

铁硫簇结合蛋白1的磁感应能力

目的探究铁硫簇结合蛋白1(ISCA1)磁场刺激后对细胞钙内流的影响。方法(1)制备携带ISCA1基因的质粒、携带Magneto 2.0序列的质粒和空载质粒,且3种质粒均携带mCherry基因,包装成慢病毒感染HEK293A细胞,荧光显微镜观察慢病毒感染效率。(2)免疫共沉淀技术检测ISCA1与隐花色素1(CRY1)和CRY2蛋白之间的结合。(3)在磁场(40 mT,0.1 Hz,90%占空比)条件下,活细胞钙成像技术检测高表达ISCA1或Magneto 2.0细胞的钙内流。结果(1)在HEK293A细胞中观察到红色荧光,表明慢病毒转染成功。(2)外源ISCA1蛋白与内源CRY1或CRY2蛋白不结合。(3)与加磁前相比,加磁后Magneto 2.0组细胞的绿色荧光强度增加(1.8±0.5)倍(P<0.05),即发生显著的钙内流;而ISCA1组及细胞对照组细胞的绿色荧光强度与加磁前相比无显著差异。结论外源高表达ISCA1的细胞在此磁场条件刺激后未引起细胞钙内流,无明显磁感应性。

FIT interacts with AtbHLH38 and AtbHLH39 in regulating iron uptake gene expression for iron homeostasis in Arabidopsis

铁是为植物生长和开发的一个必要元素。在植物的铁动态平衡紧在 transcriptional 和 posttranscriptional 水平被调整。涉及铁动态平衡的几个 bHLH 抄写因素最近被识别了。然而，他们的规章的机制仍然保持未知。在这个工作，我们证明抄写因素适合与 AtbHLH38 和 AtbHLH39 交往了并且直接在 Arabidopsis 为铁动态平衡授与铁举起基因的表示规定。在 Arabidopsis 原物的酵母二混血儿的分析和短暂表示证明那 AtbHLH38 或 AtbHLH39 交往了与合适，在 Arabidopsis 涉及铁动态平衡的一个中央抄写因素。在酵母房间的 FIT/AtbHLH38 或 FIT/AtbHLH39 的表示激活铁的螯的 reductase (FRO2 ) 和铁的 transporter (IRT1 ) 驾驶的 GUS 表示倡导者。Overexpression 与在变换的工厂的 AtbHLH38 或 AtbHLH39 合适铁举起基因 FRO2 和 IRT1 从的表示导致了到组成。因为 IRT1 蛋白质累积和高铁的螯的 reductase 活动被检测在，进一步的分析表明 FRO2 和 IRT1 没在这些工厂在 posttranscriptional 水平被调整过去在铁缺乏和铁充足下面的表示工厂。在更积累的植物在表示任何一个 AtbHLH38 上比野生型或植物在他们的射击熨的表示上双， AtbHLH39 或合适。我们铁螯的 reductase FRO2 和铁运输的 IRT1 是三个抄写因素的目标和 FRO2 和 IRT1 的抄写的数据支持被 FIT/AtbHLH38 或 FIT/AtbHLH39 的建筑群直接调整。

Evidence for a sequential transfer of iron amongst ferritin, transferrin and transferrin receptor during duodenal absorption of iron in rat and human

AIM: To elucidate the sequential transfer of iron amongst ferritin, transferrin and transferrin receptor under various iron status conditions. METHODS: Incorporation of 59Fe into mucosal and luminal proteins was carried out in control WKY rats. The sequential transfer of iron amongst ferritin, transferrin and transferrin receptor was carried out in iron deficient, control and iron overloaded rats. The duodenal proteins were subjected to immunoprecipitation and quantitation by specific ELISA and in situ localization by microautoradiography and immunohistochemistry in tandem duodenal sections. Human duodenal biopsy (n = 36) collected from subjects with differing iron status were also stained for these proteins. RESULTS: Ferritin was identified as the major protein that incorporated iron in a time-dependent manner in the duodenal mucosa. The concentration of mucosal ferritin was significantly higher in the iron excess group compared to control, iron deficient groups (731.5 ± 191.96 vs 308.3 ± 123.36, 731.5 ± 191.96 vs 256.0 ± 1.19, P < 0.005), while that of luminal transferrin which was significantly higher than the mucosal did not differ among the groups (10.9 ± 7.6 vs 0.87 ± 0.79, 11.1 ± 10.3 vs 0.80 ± 1.20, 6.8 ± 4.7 vs 0.61 ± 0.63, P < 0.001). In situ grading of proteins and iron, and their superimposition, suggested the occurrence of a sequential transfer of iron. This was demonstrated to occur through the initial binding of iron to luminal transferrin then to absorptive cell surface transferrin receptors. The staining intensity of these proteins variedaccording to the iron nutrition in humans, with intense staining of transferrin receptor observed in iron deficient subjects. CONCLUSION: It is concluded that the intestine takes up iron through a sequential transfer involving interaction of luminal transferrin, transferrin-transferrin receptor and ferritin.

Effects of Different Nitrogen Fertilizer Levels and Native Soil Properties on Rice Grain Fe, Zn and Protein Contents

Deposition of protein and metal ions （Fe, Zn） in rice grains is a complex polygenic trait showing considerable environmental effect. To analyze the effect of nitrogen application levels and native soil properties on rice grain protein, iron （Fe） and zinc （Zn） contents, 32 rice genotypes were grown at three different locations each under 80 and 120 kg/hm2 nitrogen fertilizer applications. In treatments with nitrogen fertilizer application, the brown rice grain protein content （GPC） increased significantly （1.1% to 7.0%） under higher nitrogen fertilizer application （120 kg/hm2） whereas grain Fe/Zn contents showed non-significant effect of nitrogen application level, thus suggesting that the rate of uptake and translocation of macro-elements does not influence the uptake and translocation of micro-elements. The pH, organic matter content and inherent Fe/Zn levels of native soil showed significant effects on grain Fe and Zn contents of all the rice genotypes. Grain Zn content of almost all the tested rice genotypes was found to increase at Location III having loamy soil texture, neutral pH value （pH 6.83） and higher organic matter content than the other two locations （Locations I and II）, indicating significant influence of native soil properties on brown rice grain Zn content while grain Fe content showed significant genotype × environment interaction effect. Genotypic difference was found to be the most significant factor to affect grain Fe/Zn contents in all the tested rice genotypes, indicating that although native soil properties influence phyto-availability of micronutrients and consequently influencing absorption, translocation and grain deposition of Fe/Zn ions, yet genetic makeup of a plant determines its response to varied soil conditions and other external factors. Two indica rice genotypes R-RF-31 （27.62 μg/g grain Zn content and 7.80% GPC） and R1033-968-2-1 （30.05 μg/g grain Zn content and 8.47% GPC） were identified as high grain Zn and moderate GPC rice genotypes. These results indicate that soil property and organic matter content increase the availability of Fe and Zn in rhizosphere, which in turn enhances the uptake, translocation and redistribution of Fe/Zn into rice grains.

Expression of fluorescent tagged recombinant erythroferrone protein

Objective: To produce fluorescent tagged recombinant erythroferrone protein(ERFE_eGFP) for laboratory investigations. Methods: Erythroferrone(ERFE) gene was fused to green fluorescent protein(eGFP) gene and cloned in a pSecTag2Hygro plasmid. The constructed plasmid was amplified in Escherichia coli DH5α and the eGFP-fused ERFE(ERFE_eGFP) protein was expressed in human embryonic kidney(HEK293T) cell line. Results: The plasmid constructed from colony C6 contained ERFE_eGFP with the correct restriction sizes of 4.2 kb and expressed secretory ERFE_eGFP fusion protein(approximately size of 75 kDa) in HEK293T cell line. Conclusions: ERFE_eGFP recombinant protein is successfully expressed as a secretory functional protein and could be sensitively detected using fluorometry. This fusion protein might benefit future applications for localization of cellular ERFE receptors and competitive immunoassay of ERFE concentration.

Effect of Iron Deficiency on Heterocyst Differentiation and Physiology of the Filamentous Cyanobacterium Anabaena sp. PCC 7120

The effect of iron deficiency on heterocyst differentiation and some physiological properties of the filamentous cyanobacterium Anabaena sp. PCC 7120 was investigated. Under moderate iron limitation conditions, achieved by addition of iron chelator 2,2′\|Dipyridyl (<80 μmol/L) led to delayed heterocyst differentiation, no heterocyst differentiation was observed under severe iron limitation conditions, when the concentration of 2,2′\|Dipyridyl in the medium was more than 100 μmol/L . It seemed that there are certain iron\|regulated genes or operons whose function is to control heterocyst development. In addition, iron deficiency impaired the growth. Low\|iron cells had a decrease in the quantities of pigment content (chlorophyll and phycocyanin content),the whole cell in vivo absorbance spectra confirmed the decrease, the protein electrophoretic profiles revealed that iron\|deficient cells had less protein bands, with the increase of 2,2′\|Dipyridyl ,the protein bands was more and more less. And differently, iron deficiency also caused an increase of ROS (Reactive Oxygen Species)and SOD activity, it suggests that iron deficiency led to oxidative stress, which generally occured under high\|iron conditions.

Function of the hemochromatosis protein HFE:Lessons from animal models

Hereditary hemochromatosis (HH) is caused by chronic hyperabsorption of dietary iron. Progressive accumulation of excess iron within tissue parenchymal cells may lead to severe organ damage. The most prevalent type of HH is linked to mutations in the HFE gene, encoding an atypical major histocompatibility complex classⅠmolecule. Shortly after its discovery in 1996, the hemochromatosis protein HFE was shown to physically interact with transferrin receptor 1 (TfR1) and impair the uptake of transferrin-bound iron in cells. However, these findings provided no clue why HFE mutations associate with systemic iron overload. It was later established that all forms of HH result from misregulation of hepcidin expression. This liver-derived circulating peptide hormone controls iron efflux from duodenal enterocytes and reticuloendothelial macrophages by promoting the degradation of the iron exporter ferroportin. Recent studies with animal models of HH uncover a crucial role of HFE as a hepatocyte iron sensor and upstream regulator of hepcidin. Thus, hepatocyte HFE is indispensable for signaling to hepcidin, presumably as a constituent of a larger iron-sensing complex. A working model postulates that the signaling activity of HFE is silenced when the protein is bound to TfR1. An increase in the iron saturation of plasma transferrin leads to displacement of TfR1 from HFE and assembly of the putative iron-sensing complex. In this way, iron uptake by the hepatocyte is translatedinto upregulation of hepcidin, reinforcing the concept that the liver is the major regulatory site for systemic iron homeostasis, and not merely an iron storage depot.

Tissue Carcinoembryonic Antigen,Calcium,Copper and Iron Levels in Cancerous Lung Patients

Background and objective The expression of various trace elements and markers in lung cancer is controversial.The aim of this study is to evaluate the presence of calcium(Ca),copper(Cu),iron(Fe) and carcinoembryonic antigen(CEA) in cancerous untreated lung tissues and to determine a possible association between these markers and lung cancer.Methods Fourty-eight cancerous lung tissue blocks,from Sultan Qaboos University Hospital,Sultanate of Oman,were studied.Fe,Ca,Cu,and CEA were demonstrated in the tissue blocks using Perl's Prussian blue,Von Kossa's,modified rhodanine and immunohistochemical staining methods,respectively.Results Twenty-three of 48 specimens showed positive Fe staining,2 showed positive Ca staining and Cu was absent in all specimens.93.7% expressed CEA in varying degree of positivity.81.25% of these sections showed high expression of CEA.Conclusion Tissue concentrations of trace elements were not elevated in lung cancer and therefore cannot be considered as a potential marker.Despite the low sensitivity and specificity of CEA as previously reported,tissue CEA should be considered as a potential marker in the evaluation of lung cancer.

Influence of the Environment on Cassava Quality Traits in Central Rift Valley of Kenya

Cassava (Manihot esculenta Cranzt) is an important food security crop for poor rural communities particularly in Africa. However, little is known about variability of critical root nutritional and quality traits of African cassava germplasm. Cassava roots contain low levels of important micronutrients and its quality can be influenced by the levels of cyanogenic glucosides. Roots from fourteen accessions comprising Kenyan local landraces and improved clones were screened for their nutritional traits including the contents of cyanogenic glycosides, protein and the micro nutrients iron and zinc. Trait stability and the effects of the environment on the expression of the nutritional traits were evaluated using various genotype (G) by environment (E) interaction study models. There were significant (p ≤ 0.05) differences for all the nutritional traits in the three test sites of Baringo, Kericho and Nakuru in Kenya. Contents of cyanogenic glycosides in both roots and leaves, total root proteins, root iron and zinc ranged from 31.8 ppm to 90.8 ppm;20.8 ppm to 154.4 ppm;1.15% to 3.47%;17.81 ppm to 59.69 ppm and 39.39 ppm to 118 ppm, respectively. The sites were also significantly (p ≤ 0.05) different from each other with the highest cyanogenic content in leaves and roots expressed at the Nakuru site. Regression analysis was used to assess genotype response to environments. Regression coefficients (bi) obtained ranged from 0.13 to 2.23 for all traits combined indicating wide variability in quality trait among the test germplasm. Analysis for sensitivity to environmental change SEi2 revealed that cassava genotypes differed in their level of sensitivity. The root cyanide trait had the highest mean SEi2 which indicated that it was the least stable quality trait in the cassava germplasm. This implies that the same cassava genotypes will give food of different quality depending on growing environment. The observed values for protein and mineral contents suggest the potential for improving the nutritive value of local cassava germplasm.

Optimization of Chelation Process for Complex Microelement Iron Supplement Derived from Pig Blood by Response Surface Methodology

[Objectives]This study aimed to optimize the chelation process for complex microelement iron supplement derived from pig blood by response surface methodology.[Methods]On the basis of single-factor test,p H value,concentration of polypeptide solution and volume ratio of polypeptide solution to FeCl_2 solution were selected as influencing factors with Fe(II)chelation rate as the indicator for Box-Behnken central composite experimental design with three factors and three levels.The effects of three factors on the response value were analyzed by response surface methodology.[Results]The optimized chelation process for complex microelement iron supplement derived from pig blood by response surface methodology was as follows:pH 5.40,polypeptide solution concentration 2.27%,volume ratio of polypeptide solution to FeCl_2 solution 2.16∶1.Under this condition,the predictive Fe(II)chelation rate of iron supplement was 79.37%,while the actual value was 79.41%.[Conclusions]The optimized process may provide new thoughts for the development and utilization of complex microelement iron supplement derived from pig blood.