AIM:To compare iron depletion to lifestyle changes alone in patients with severe nonalcoholic fatty liver disease(NAFLD)and hyperferritinemia,a frequent feature associated with more severe liver damage,despite at leas...AIM:To compare iron depletion to lifestyle changes alone in patients with severe nonalcoholic fatty liver disease(NAFLD)and hyperferritinemia,a frequent feature associated with more severe liver damage,despite at least 6 mo of lifestyle changes.METHODS:Eligible subjects had to be 18-75 years old who underwent liver biopsy for ultrasonographically detected liver steatosis and hyperferritinemia,ferritin levels≥250 ng/mL,and NAFLD activity score>1.Iron depletion had to be achieved by removing 350 cc of blood every 10-15 d according to baseline hemoglobin values and venesection tolerance,until ferritin<30 ng/mL and/or transferrin saturation(TS)<25%.Thirty-eight patients were randomized 1:1 to phlebotomy(n=21)or lifestyle changes alone(n=17).The main outcome of the study was improvement in liver damage according to the NAFLD activity score at 2 years,secondary outcomes were improvements in liver enzymes[alanine aminotransferases(ALT),aspartate aminotransferase(AST),and gamma-glutamyl-transferases(GGT)].RESULTS:Phlebotomy was associated with normalization of iron parameters without adverse events.In the21 patients compliant to the study protocol,the rate of histological improvement was higher in iron depleted vs control subjects(8/12,67%vs 2/9,22%,P=0.039).There was a better improvement in steatosis grade in iron depleted vs control patients(P=0.02).In patients followed-up at two years(n=35),ALT,AST,and GGT levels were lower in iron-depleted than in control patients(P<0.05).The prevalence of subjects with improvement in histological damage or,in the absence of liver biopsy,ALT decrease≥20%(associated with histological improvement in biopsied patients)was higher in the phlebotomy than in the control arm(P=0.022).The effect of iron depletion on liver damage improvement as assessed by histology or ALT decrease≥20%was independent of baseline AST/ALT ratio and insulin resistance(P=0.0001).CONCLUSION:Iron depletion by phlebotomy is likely associated with a higher rate of improvement of histological liver damage than lifestyle changes alone in patients with NAFLD and hyperferritinemia,and with amelioration of liver enzymes.展开更多
Effect of Fe nutrition on Fe acquisition, aconitase enzyme activity and assimilation of the element in ferritin protein was studied in two indica rice cultivars viz. Sharbati and Lalat having contrasting grain Fe conc...Effect of Fe nutrition on Fe acquisition, aconitase enzyme activity and assimilation of the element in ferritin protein was studied in two indica rice cultivars viz. Sharbati and Lalat having contrasting grain Fe concentration. Young rice seedlings were grown in hydroponics with different levels of Fe. For comparison, the two cultivars were also grown in the field under natural conditions of rice culture. Iron accumulation, aconitase activity and ferritin level were higher in the high Fe containing cultivar, Sharbati than that in the low Fe containing cultivar, Lalat. While aconitase activity increased consistently with the increase in concentration of Fe in the growing medium, the same was not found to be true for accumulation of ferritin protein. The leaf ferritin level increased up to a certain level of Fe in the growing medium and declined thereafter. Levels of Fe in the growing medium giving maximum ferritin synthesis were found to be different in the two rice cultivars. In both cultivars, aconitase activity attained maximum level after 20 days of panicle emergence (heading). Pattern of Fe accumulation in the leaves in response to increasing Fe level in the nutrient solution paralleled with that of the aconitase activity indicating a positive correlation. It was concluded that accumulation of both ferritin protein and aconitase enzyme were influenced not only by the Fe level in the growing medium but also by the internal Fe concentration of the two cultivars.展开更多
A total of 105 transgenic dce lines independently transformed with a pea ferritin gene （Fer） were previously obtained. After seven generations of selfing and β-glucuronidase （GUS） assisted selection, 82 transgeni...A total of 105 transgenic dce lines independently transformed with a pea ferritin gene （Fer） were previously obtained. After seven generations of selfing and β-glucuronidase （GUS） assisted selection, 82 transgenic lines with stable agronomic traits were got. Among the 82 transgenic lines, two high-iron transgenic rice lines Fer34 and Fer65, with the iron contents in the milled rice being 4.82 and 3.46 times of that of the wild type Xiushui 11, respectively were identified. In the two transgenic lines, the exogenous Fer gene was highly expressed, and inherited as a single locus. The transgene had no negative effect on the agronomic traits of rice plant, other mineral nutritional components, appearance quality and eating quality of the milled rice, indicating that these two lines were elite high-iron breeding lines. Furthermore, the practical application and further studies facilitating utilization of the two elite breeding lines were discussed.展开更多
AIM:To study the role of hepcidin in hereditary hyperferritinemia cataract syndrome(HHCS). METHODS:Six patients from two families with HHCS, confirmed by genetic analysis showing A to G mutation at position+40 in the ...AIM:To study the role of hepcidin in hereditary hyperferritinemia cataract syndrome(HHCS). METHODS:Six patients from two families with HHCS, confirmed by genetic analysis showing A to G mutation at position+40 in the L-ferritin gene,were recruited to undergo serum hepcidin and prohepcidin measurements using radioimmunoassay and enzyme linked immunoassay,respectively,and measurements were compared with levels in serum from 25 healthy volunteers(14 females),mean age 36±11.9 years.RESULTS:The serum hepcidin and prohepcidin levels in patients with HHCS were 19.1±18.6 and 187± 120.9 ng/mL,respectively.Serum ferritin was 1716.3± 376μg/L.Liver biopsy in one patient did not show any evidence of iron overload.Serum hepcidin and prohepcidin values in healthy controls(HCs)were 15.30±15.71 and 236.88±83.68 ng/mL,respectively,while serum ferritin was 110±128.08μg/L.There was no statistical difference in serum hepcidin level between the two cohorts(19.1±18.6 ng/mL vs 15.30±15.71 ng/mL,P= 0.612)using two-tailed t-test. CONCLUSION:Serum hepcidin levels in HHCS patients is similar to that in HCs.Our study suggests that circulating ferritin is not a factor influencing hepcidin synthesis and does not have a role in the iron-sensing mechanism in hepatocytes.展开更多
Nonalcoholic fatty liver disease(NAFLD),defined by excessive liver fat deposition related to the metabolic syndrome,is a leading cause of progressive liver disease,for which accurate non-invasive staging systems and e...Nonalcoholic fatty liver disease(NAFLD),defined by excessive liver fat deposition related to the metabolic syndrome,is a leading cause of progressive liver disease,for which accurate non-invasive staging systems and effective treatments are still lacking.Evidence has shown that increased ferritin levels are associated with the metabolic insulin resistance syndrome,and higher hepatic iron and fat content.Hyperferritinemia and iron stores have been associated with the severity of liver damage in NAFLD,and iron depletion reduced insulin resistance and liver enzymes.Recently,Kowdley et al demonstrated in a multicenter study in 628 adult patients with NAFLD from the NAFLD-clinical research network database with central re-evaluation of liver histology and iron staining that the increased serum ferritin level is an independent predictor of liver damage in patients with NAFLD,and is useful to identify NAFLD patients at risk of non-alcoholic steatohepatitis and advanced fibrosis.These data indicate that incorporation of serum ferritin level may improve the performance of noninvasive scoring of liver damage in patients with NAFLD,and that iron depletion still represents an attractive therapeutic target to prevent the progression of liver damage in these patients.展开更多
Anemia is a common extraintestinal manifestation of inflammatory bowel disease(IBD) and is frequently overlooked as a complication. Patients with IBD are commonly found to have iron deficiency anemia(IDA) secondary to...Anemia is a common extraintestinal manifestation of inflammatory bowel disease(IBD) and is frequently overlooked as a complication. Patients with IBD are commonly found to have iron deficiency anemia(IDA) secondary to chronic blood loss, and impaired iron absorption due to tissue inflammation. Patients with iron deficiency may not always manifest with signs and symptoms; so, hemoglobin levels in patients with IBD must be regularly monitored for earlier detection of anemia. IDA in IBD is associated with poor quality of life, necessitating prompt diagnosis and appropriate treatment. IDA is often associated with inflammation in patients with IBD. Thus, commonly used labora-tory parameters are inadequate to diagnose IDA, and newer iron indices, such as reticulocyte hemoglobin content or percentage of hypochromic red cells or zinc protoporphyrin, are required to differentiate IDA from anemia of chronic disease. Oral iron preparations are available and are used in patients with mild disease activity. These preparations are inexpensive and con-venient, but can produce gastrointestinal side effects, such as abdominal pain and diarrhea, that limit their use and patient compliance. These preparations are partly absorbed due to inflammation. Non-absorbed iron can be toxic and worsen IBD disease activity. Although cost-effective intravenous iron formulations are widely available and have improved safety profiles, physicians are reluctant to use them. We present a review of the pathophysiologic mechanisms of IDA in IBD, improved diagnostic and therapeutic strategies, efficacy, and safety of iron replacement in IBD.展开更多
Ferritin, a universal intracellular protein, can store large amounts of iron and improve plant resistance to abiotic and biotic stress. In this study, a ferritin gene(TaFer) from Tamarix androssowii Litv. was transfer...Ferritin, a universal intracellular protein, can store large amounts of iron and improve plant resistance to abiotic and biotic stress. In this study, a ferritin gene(TaFer) from Tamarix androssowii Litv. was transferred into Populus tomentosa Carr. cv 'BJR01' via Agrobacterium. Six independent transgenic lines were obtained with a tolerance to kanamycin and three were randomly selected for further analysis. The PCR and RT-PCR results indicate that the TaFer gene had been integrated into the poplar genome. The effect of the gene on abiotic stress tolerance was tested, and the results show that transgenic plants improve growth, had higher chlorophyll and lower MDA contents, and higher relative electrical conductivity,fewer changes of SOD and POD activities, higher iron content, higher root ferric reductase activity and lower levels of ROS accumulation and cell death in response to drought, Fe-insufficient or Fe-excess tolerance. These results indicate that the TaFer gene can improve abiotic stress tolerance in transgenic Populus tomentosa.展开更多
Iron is an essential trophic element that is required for cell viability and differentiation, especially in oligodendrocytes, which consume relatively high rates of energy to produce myelin. Multiple iron metabolism p...Iron is an essential trophic element that is required for cell viability and differentiation, especially in oligodendrocytes, which consume relatively high rates of energy to produce myelin. Multiple iron metabolism proteins are expressed in the brain including transferrin receptor and ferritin-H. However, it is still unknown whether they are developmentally regulated in oligodendrocyte lineage cells for myelination. Here, using an in vitro cultured differentiation model of oligodendrocytes, we found that both transferrin receptor and ferritin-H are significantly upregulated during oligodendrocyte maturation, implying the essential role of iron in the development of oligodendrocytes. Additional different doses of Fe3＋ in the cultured medium did not affect oligodendrocyte precursor cell maturation or ferritin-H expression but decreased the expression of the transferrin receptor. These results indicate that upregulation of both transferrin receptor and ferritin-H contributes to maturation and myelination of oligodendrocyte precursor cells.展开更多
Background: Anemia is one of the complications of chronic kidney disease (CKD) which necessitates multiple blood transfusions. These multiple transfusions are usually accompanied by Iron over load. The current study a...Background: Anemia is one of the complications of chronic kidney disease (CKD) which necessitates multiple blood transfusions. These multiple transfusions are usually accompanied by Iron over load. The current study aimed to assess the Iron profile in Sudanese patients with chronic renal failure received regular blood transfused. Materials and Methods: A descriptive analytical case control study was performed in Alturki Teaching Hospital, Khartoum, Sudan. A total of 90 Sudanese were enrolled in this study (30 CKD patients under hemodialysis and undergo multiple blood transfusion, 30 CKD patients under hemodialysis but not blood transfusion and 30 healthy controls, 51 (57%) were male and 39 (43%) were females, their age ranged between 28 to 75 years. Iron profile (serum iron, serum ferritin and total iron binding capacity (TIBC)) were measured using full automated Chemical analyzer Mindray BS 200 (China). Data were analyzed by using statistical package for social sciences (SPSS) verssion16. Results: The present study showed that serum iron and serum ferritin of those under hemodialysis and received regular blood transfusion patient were significantly higher compared to those under hemodialysis and did not received regular blood transfusion patients (P value 0.000 and 0.01) respectively. Conclusion: Patients with chronic renal failure and under hemodialysis and receive regular and multiple transfusions are prone to iron overload.展开更多
基金Supported by Associazione Malattie Metaboliche del Fegato ONLUS(Non-profit organization for the Study and Care of Metabolic Liver Diseases),Centro Studi Malattie Metaboliche del Fegato,Universitàdegli Studi di Milano
文摘AIM:To compare iron depletion to lifestyle changes alone in patients with severe nonalcoholic fatty liver disease(NAFLD)and hyperferritinemia,a frequent feature associated with more severe liver damage,despite at least 6 mo of lifestyle changes.METHODS:Eligible subjects had to be 18-75 years old who underwent liver biopsy for ultrasonographically detected liver steatosis and hyperferritinemia,ferritin levels≥250 ng/mL,and NAFLD activity score>1.Iron depletion had to be achieved by removing 350 cc of blood every 10-15 d according to baseline hemoglobin values and venesection tolerance,until ferritin<30 ng/mL and/or transferrin saturation(TS)<25%.Thirty-eight patients were randomized 1:1 to phlebotomy(n=21)or lifestyle changes alone(n=17).The main outcome of the study was improvement in liver damage according to the NAFLD activity score at 2 years,secondary outcomes were improvements in liver enzymes[alanine aminotransferases(ALT),aspartate aminotransferase(AST),and gamma-glutamyl-transferases(GGT)].RESULTS:Phlebotomy was associated with normalization of iron parameters without adverse events.In the21 patients compliant to the study protocol,the rate of histological improvement was higher in iron depleted vs control subjects(8/12,67%vs 2/9,22%,P=0.039).There was a better improvement in steatosis grade in iron depleted vs control patients(P=0.02).In patients followed-up at two years(n=35),ALT,AST,and GGT levels were lower in iron-depleted than in control patients(P<0.05).The prevalence of subjects with improvement in histological damage or,in the absence of liver biopsy,ALT decrease≥20%(associated with histological improvement in biopsied patients)was higher in the phlebotomy than in the control arm(P=0.022).The effect of iron depletion on liver damage improvement as assessed by histology or ALT decrease≥20%was independent of baseline AST/ALT ratio and insulin resistance(P=0.0001).CONCLUSION:Iron depletion by phlebotomy is likely associated with a higher rate of improvement of histological liver damage than lifestyle changes alone in patients with NAFLD and hyperferritinemia,and with amelioration of liver enzymes.
文摘Effect of Fe nutrition on Fe acquisition, aconitase enzyme activity and assimilation of the element in ferritin protein was studied in two indica rice cultivars viz. Sharbati and Lalat having contrasting grain Fe concentration. Young rice seedlings were grown in hydroponics with different levels of Fe. For comparison, the two cultivars were also grown in the field under natural conditions of rice culture. Iron accumulation, aconitase activity and ferritin level were higher in the high Fe containing cultivar, Sharbati than that in the low Fe containing cultivar, Lalat. While aconitase activity increased consistently with the increase in concentration of Fe in the growing medium, the same was not found to be true for accumulation of ferritin protein. The leaf ferritin level increased up to a certain level of Fe in the growing medium and declined thereafter. Levels of Fe in the growing medium giving maximum ferritin synthesis were found to be different in the two rice cultivars. In both cultivars, aconitase activity attained maximum level after 20 days of panicle emergence (heading). Pattern of Fe accumulation in the leaves in response to increasing Fe level in the nutrient solution paralleled with that of the aconitase activity indicating a positive correlation. It was concluded that accumulation of both ferritin protein and aconitase enzyme were influenced not only by the Fe level in the growing medium but also by the internal Fe concentration of the two cultivars.
文摘A total of 105 transgenic dce lines independently transformed with a pea ferritin gene （Fer） were previously obtained. After seven generations of selfing and β-glucuronidase （GUS） assisted selection, 82 transgenic lines with stable agronomic traits were got. Among the 82 transgenic lines, two high-iron transgenic rice lines Fer34 and Fer65, with the iron contents in the milled rice being 4.82 and 3.46 times of that of the wild type Xiushui 11, respectively were identified. In the two transgenic lines, the exogenous Fer gene was highly expressed, and inherited as a single locus. The transgene had no negative effect on the agronomic traits of rice plant, other mineral nutritional components, appearance quality and eating quality of the milled rice, indicating that these two lines were elite high-iron breeding lines. Furthermore, the practical application and further studies facilitating utilization of the two elite breeding lines were discussed.
基金Supported by Research and Development Department,Ealing Hospital NHS Trust,Uxbridge Road,Southall,London,UB13HW,United Kingdom
文摘AIM:To study the role of hepcidin in hereditary hyperferritinemia cataract syndrome(HHCS). METHODS:Six patients from two families with HHCS, confirmed by genetic analysis showing A to G mutation at position+40 in the L-ferritin gene,were recruited to undergo serum hepcidin and prohepcidin measurements using radioimmunoassay and enzyme linked immunoassay,respectively,and measurements were compared with levels in serum from 25 healthy volunteers(14 females),mean age 36±11.9 years.RESULTS:The serum hepcidin and prohepcidin levels in patients with HHCS were 19.1±18.6 and 187± 120.9 ng/mL,respectively.Serum ferritin was 1716.3± 376μg/L.Liver biopsy in one patient did not show any evidence of iron overload.Serum hepcidin and prohepcidin values in healthy controls(HCs)were 15.30±15.71 and 236.88±83.68 ng/mL,respectively,while serum ferritin was 110±128.08μg/L.There was no statistical difference in serum hepcidin level between the two cohorts(19.1±18.6 ng/mL vs 15.30±15.71 ng/mL,P= 0.612)using two-tailed t-test. CONCLUSION:Serum hepcidin levels in HHCS patients is similar to that in HCs.Our study suggests that circulating ferritin is not a factor influencing hepcidin synthesis and does not have a role in the iron-sensing mechanism in hepatocytes.
基金Supported by First Università degli Studi di Milano 2007,2008,to Valenti L and Fargion SRicerca corrente Ospedale Maggiore Policlinico 2006 and 2008,to Valenti L and FargionSCentro per lo Studio delle Malattie del Fegato e del Metabolismo
文摘Nonalcoholic fatty liver disease(NAFLD),defined by excessive liver fat deposition related to the metabolic syndrome,is a leading cause of progressive liver disease,for which accurate non-invasive staging systems and effective treatments are still lacking.Evidence has shown that increased ferritin levels are associated with the metabolic insulin resistance syndrome,and higher hepatic iron and fat content.Hyperferritinemia and iron stores have been associated with the severity of liver damage in NAFLD,and iron depletion reduced insulin resistance and liver enzymes.Recently,Kowdley et al demonstrated in a multicenter study in 628 adult patients with NAFLD from the NAFLD-clinical research network database with central re-evaluation of liver histology and iron staining that the increased serum ferritin level is an independent predictor of liver damage in patients with NAFLD,and is useful to identify NAFLD patients at risk of non-alcoholic steatohepatitis and advanced fibrosis.These data indicate that incorporation of serum ferritin level may improve the performance of noninvasive scoring of liver damage in patients with NAFLD,and that iron depletion still represents an attractive therapeutic target to prevent the progression of liver damage in these patients.
文摘Anemia is a common extraintestinal manifestation of inflammatory bowel disease(IBD) and is frequently overlooked as a complication. Patients with IBD are commonly found to have iron deficiency anemia(IDA) secondary to chronic blood loss, and impaired iron absorption due to tissue inflammation. Patients with iron deficiency may not always manifest with signs and symptoms; so, hemoglobin levels in patients with IBD must be regularly monitored for earlier detection of anemia. IDA in IBD is associated with poor quality of life, necessitating prompt diagnosis and appropriate treatment. IDA is often associated with inflammation in patients with IBD. Thus, commonly used labora-tory parameters are inadequate to diagnose IDA, and newer iron indices, such as reticulocyte hemoglobin content or percentage of hypochromic red cells or zinc protoporphyrin, are required to differentiate IDA from anemia of chronic disease. Oral iron preparations are available and are used in patients with mild disease activity. These preparations are inexpensive and con-venient, but can produce gastrointestinal side effects, such as abdominal pain and diarrhea, that limit their use and patient compliance. These preparations are partly absorbed due to inflammation. Non-absorbed iron can be toxic and worsen IBD disease activity. Although cost-effective intravenous iron formulations are widely available and have improved safety profiles, physicians are reluctant to use them. We present a review of the pathophysiologic mechanisms of IDA in IBD, improved diagnostic and therapeutic strategies, efficacy, and safety of iron replacement in IBD.
基金supported by Hi-Tech Research and Development Program of China(2013AA102701)Excellent Creative Talents Supporting Program of Heilongjiang University of Chinese Medicine(2012RCQ24)
文摘Ferritin, a universal intracellular protein, can store large amounts of iron and improve plant resistance to abiotic and biotic stress. In this study, a ferritin gene(TaFer) from Tamarix androssowii Litv. was transferred into Populus tomentosa Carr. cv 'BJR01' via Agrobacterium. Six independent transgenic lines were obtained with a tolerance to kanamycin and three were randomly selected for further analysis. The PCR and RT-PCR results indicate that the TaFer gene had been integrated into the poplar genome. The effect of the gene on abiotic stress tolerance was tested, and the results show that transgenic plants improve growth, had higher chlorophyll and lower MDA contents, and higher relative electrical conductivity,fewer changes of SOD and POD activities, higher iron content, higher root ferric reductase activity and lower levels of ROS accumulation and cell death in response to drought, Fe-insufficient or Fe-excess tolerance. These results indicate that the TaFer gene can improve abiotic stress tolerance in transgenic Populus tomentosa.
基金funded by Shanghai Municipal Health Bureau,No.KPB-WSJ1004the National Natural Science Foundation of China,No.81200971
文摘Iron is an essential trophic element that is required for cell viability and differentiation, especially in oligodendrocytes, which consume relatively high rates of energy to produce myelin. Multiple iron metabolism proteins are expressed in the brain including transferrin receptor and ferritin-H. However, it is still unknown whether they are developmentally regulated in oligodendrocyte lineage cells for myelination. Here, using an in vitro cultured differentiation model of oligodendrocytes, we found that both transferrin receptor and ferritin-H are significantly upregulated during oligodendrocyte maturation, implying the essential role of iron in the development of oligodendrocytes. Additional different doses of Fe3＋ in the cultured medium did not affect oligodendrocyte precursor cell maturation or ferritin-H expression but decreased the expression of the transferrin receptor. These results indicate that upregulation of both transferrin receptor and ferritin-H contributes to maturation and myelination of oligodendrocyte precursor cells.
文摘Background: Anemia is one of the complications of chronic kidney disease (CKD) which necessitates multiple blood transfusions. These multiple transfusions are usually accompanied by Iron over load. The current study aimed to assess the Iron profile in Sudanese patients with chronic renal failure received regular blood transfused. Materials and Methods: A descriptive analytical case control study was performed in Alturki Teaching Hospital, Khartoum, Sudan. A total of 90 Sudanese were enrolled in this study (30 CKD patients under hemodialysis and undergo multiple blood transfusion, 30 CKD patients under hemodialysis but not blood transfusion and 30 healthy controls, 51 (57%) were male and 39 (43%) were females, their age ranged between 28 to 75 years. Iron profile (serum iron, serum ferritin and total iron binding capacity (TIBC)) were measured using full automated Chemical analyzer Mindray BS 200 (China). Data were analyzed by using statistical package for social sciences (SPSS) verssion16. Results: The present study showed that serum iron and serum ferritin of those under hemodialysis and received regular blood transfusion patient were significantly higher compared to those under hemodialysis and did not received regular blood transfusion patients (P value 0.000 and 0.01) respectively. Conclusion: Patients with chronic renal failure and under hemodialysis and receive regular and multiple transfusions are prone to iron overload.
