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Plasma non-transferrin-bound iron uptake by the small intestine leads to intestinal injury and intestinal flora dysbiosis in an iron overload mouse model and Caco-2 cells
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作者 Qian Zhang Haoxuan Ding +4 位作者 Xiaonan Yu Qiwen Wang Xuejiao Li Ruiqiang Zhang Jie Feng 《Science China(Life Sciences)》 SCIE CAS CSCD 2023年第9期2041-2055,共15页
Iron overload often occurs during blood transfusion and iron supplementation, resulting in the presence of non-transferrin-bound iron(NTBI) in host plasma and damage to multiple organs, but effects on the intestine ha... Iron overload often occurs during blood transfusion and iron supplementation, resulting in the presence of non-transferrin-bound iron(NTBI) in host plasma and damage to multiple organs, but effects on the intestine have rarely been reported. In this study, an iron overload mouse model with plasma NTBI was established by intraperitoneal injection of iron dextran. We found that plasma NTBI damaged intestinal morphology, caused intestinal oxidative stress injury and reactive oxygen species(ROS) accumulation,and induced intestinal epithelial cell apoptosis. In addition, plasma NTBI increased the relative abundance of Ileibacterium and Desulfovibrio in the cecum, while the relative abundance of Faecalibaculum and Romboutsia was reduced. Ileibacterium may be a potential microbial biomarker of plasma NTBI. Based on the function prediction analysis, plasma NTBI led to the weakening of intestinal microbiota function, significantly reducing the function of the extracellular structure. Further investigation into the mechanism of injury showed that iron absorption in the small intestine significantly increased in the iron group. Caco-2 cell monolayers were used as a model of the intestinal epithelium to study the mechanism of iron transport. By adding ferric ammonium citrate(FAC, plasma NTBI in physiological form) to the basolateral side, the apparent permeability coefficient(Papp) values from the basolateral to the apical side were greater than 3×10^(-6)cm s^(-1). Intracellular ferritin level and apical iron concentration significantly increased, and SLC39A8(ZIP8) and SLC39A14(ZIP14) were highly expressed in the FAC group.Short hairpin RNA(sh RNA) was used to knock down ZIP8 and ZIP14 in Caco-2 cells. Transfection with ZIP14-specific sh RNA decreased intracellular ferritin level and inhibited iron uptake. These results revealed that plasma NTBI may cause intestinal injury and intestinal flora dysbiosis due to the uptake of plasma NTBI from the basolateral side into the small intestine, which is probably mediated by ZIP14. 展开更多
关键词 iron overload non-transferrin-bound iron intestinal injury intestinal flora dysbiosis iron transporter
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Early detection of cardiac involvement in thalassemia: From bench to bedside perspective 被引量:1
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作者 Nut Koonrungsesomboon Siriporn C Chattipakorn +1 位作者 Suthat Fucharoen Nipon Chattipakorn 《World Journal of Cardiology》 CAS 2013年第8期270-279,共10页
Myocardial siderosis is known as the major cause of death in thalassemia major(TM) patients since it can lead to iron overload cardiomyopathy.Although this condition can be prevented if timely effective intensive chel... Myocardial siderosis is known as the major cause of death in thalassemia major(TM) patients since it can lead to iron overload cardiomyopathy.Although this condition can be prevented if timely effective intensive chelation is given to patients,the mortality rate of iron overload cardiomyopathy still remains high due to late detection of this condition.Various direct and indirect methods of iron assessment,including serum ferritin level,echocardiogram,non-transferrin-bound iron,cardiac magnetic resonance T2*,heart rate variability,and liver biopsy and myocardial biopsy,have been proposed for early detection of cardiac iron overload in TM patients.However,controversial evidence and limitations of their use in clinical practice exist.In this review article,all of these iron assessment methods that have been proposed or used to directly or indirectly determine the cardiac iron status in TM reported from both basic and clinical studies are comprehensively summarized and presented.Since there has been growing evidence in the past decades that cardiac magnetic resonance imaging as well as cardiac autonomic status known as the heart rate variability can provide early detection of cardiac involvement in TM patients,these two methods are also presented and discussed.The existing controversy regarding the assessment of cardiac involvement in thalassemia is also discussed. 展开更多
关键词 THALASSEMIA IRON overload CARDIOMYOPATHY Serum FERRITIN Heart rate variability Magnetic resonance non-transferrin-bound IRON
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黑素转铁蛋白在家兔网织红细胞膜上的表达及其在铁摄取中的作用
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作者 陈文芳 钱忠明 谢俊霞 《中国应用生理学杂志》 CAS CSCD 北大核心 2001年第4期356-359,共4页
目的 :研究黑素转铁蛋白 (p97)在家兔网织红细胞膜上的表达及其在非转铁蛋白结合铁摄取中的作用。方法 :聚丙烯酰胺凝胶电泳 (SDS =PAGE)和放射性同位素法 (59Fe)。结果 :①网织红细胞孵育液浓缩后 ,经SDS PAGE测定 ,在分子量 97kD位置... 目的 :研究黑素转铁蛋白 (p97)在家兔网织红细胞膜上的表达及其在非转铁蛋白结合铁摄取中的作用。方法 :聚丙烯酰胺凝胶电泳 (SDS =PAGE)和放射性同位素法 (59Fe)。结果 :①网织红细胞孵育液浓缩后 ,经SDS PAGE测定 ,在分子量 97kD位置上可见一条明显的蛋白带 ;用磷脂酚肌醇磷脂酶C(PI PLC) 30 0mu/ml预处理网织红细胞后 ,孵育液浓缩再经SDS PAGE测定 ,在分子量 97kD处仍有一条明显的蛋白带 ,且其平均OD值高于未经处理的网织红细胞 ;而成熟的红细胞在此处却没有明显的蛋白带。②单纯用PI PLC作用于网织红细胞 ,其铁摄取无明显变化 (P >0 .0 5 )。③去除内源性转铁蛋白后 ,再用PI PLC作用网织红细胞 ,则胞浆内铁及整合到血红素中的铁均较未经处理的网织红细胞明显降低 (P <0 .0 5 )。结论 :p97可能存在于家兔网织红细胞膜上 。 展开更多
关键词 黑素转铁蛋白 聚丙烯酚胺凝胶电泳 非转铁蛋白结合铁 网织红细胞膜 铁摄取
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Iron-chelating and anti-lipid peroxidation properties of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one(CM1)in longterm iron loading β-thalassemic mice
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作者 Kanokwan Kulprachakarn Nittaya Chansiw +5 位作者 Kanjana Pangjit Chada Phisalaphong Suthat Fucharoen Robert C.Hider Sineenart Santitherakul Somdet Srichairatanakool 《Asian Pacific Journal of Tropical Biomedicine》 SCIE CAS 2014年第8期663-668,共6页
Objective:To evaluate the iron—chelating properties and free—radical scavenging activities of1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methyIpyridin—4-one(CM1) treatment in chronic iron-loaded β-thalassemic(BKO) mice.... Objective:To evaluate the iron—chelating properties and free—radical scavenging activities of1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methyIpyridin—4-one(CM1) treatment in chronic iron-loaded β-thalassemic(BKO) mice.Methods:The BKO mice were fed with a ferrocene-rich diet and were orally administered with CM1|50 mg/(kg·day)| for 6 months.Blood levels of non-transferrin hound iron,labile plasma iron.ferritin(Ft) and malondialdehyde were determined.Results:The BKO mice were fed with an iron diet for 8 months which resulted in iron overload.Interestingly,the mice showed a decrease in the non—transferrin bound iron,labile plasma iron and malondialdehyde levels,but not the Ft levels after continuous CM1 treatment.Conclusions:CM1 could be an effective oral iron chelator that can reduce iron overload and lipid peroxidation in chronic iron overload β—thalassemic mice. 展开更多
关键词 Iron-chelating IRON overload Β-THALASSEMIA IRON CHELATOR Non-transferrin bound IRON Lipid peroxidation
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