AIM To studied iron metabolism in liver, spleen, and serum after acute liver-damage, in relation to surrogate markers for liver-damage and repair.METHODS Rats received intraperitoneal injection of the hepatotoxin thio...AIM To studied iron metabolism in liver, spleen, and serum after acute liver-damage, in relation to surrogate markers for liver-damage and repair.METHODS Rats received intraperitoneal injection of the hepatotoxin thioacetamide(TAA), and were sacrificed regularly between 1 and 96 h thereafter. Serum levels of transaminases and iron were measured using conventional laboratory assays. Liver tissue was used for conventional histology, immunohistology, and iron staining. The expression of acute-phase cytokines, ferritin light chain(FTL), and ferritin heavy chain(FTH)was investigated in the liver by q RT-PCR. Western blotting was used to investigate FTL and FTH in liver tissue and serum. Liver and spleen tissue was also used to determine iron concentrations.RESULTS After a short initial decrease, iron serum concentrations increased in parallel with serum transaminase(aspartate aminotransferase and alanine aminotransferase) levels, which reached a maximum at 48 h, and decreased thereafter. Similarly, after 48 h a significant increase in FTL, and after 72 h in FTH was detected in serum. While earliest morphological signs of inflammation in liver were visible after 6 h, increased expression of the two acute-phase cytokines IFN-γ(1 h) and IL-1β(3 h) was detectable earlier, with maximum values after 12-24 h. Iron concentrations in liver tissue increased steadily between 1 h and 48 h, and remained high at 96 h. In contrast, spleen iron concentrations remained unchanged until 48 h, and increased mildly thereafter(96 h). Although tissue iron staining was negative, hepatic FTL and FTH protein levels were strongly elevated. Our results reveal effects on hepatic iron concentrations after direct liver injury by TAA. The increase of liver iron concentrations may be due to the uptake of a significant proportion of the metal by healthy hepatocytes, and only to a minor extent by macrophages, as spleen iron concentrations do not increase in parallel. The temporary increase of iron, FTH and transaminases in serum is obviously due to their release by damaged hepatocytes.CONCLUSION Increased liver iron levels may be the consequence of hepatocyte damage. Iron released into serum by damaged hepatocytes is obviously transported back and stored via ferritins.展开更多
Ferritin,an iron-storage protein,regulates cellular iron metabolism and oxidative stress.The ferritin structure is characterized as a spherical cage,inside which large amounts of iron are deposited in a safe,compact a...Ferritin,an iron-storage protein,regulates cellular iron metabolism and oxidative stress.The ferritin structure is characterized as a spherical cage,inside which large amounts of iron are deposited in a safe,compact and bioavailable form.All ferritins readily catalyze Fe(II)oxidation by peroxides at the ferroxidase center to prevent free Fe(II)from participating in oxygen free radical formation via Fenton chemistry.Thus,ferritin is generally recognized as a cytoprotective stratagem against intracellular oxidative damage.The expression of cytosolic ferritins is usually regulated by iron status and oxidative stress at both the transcriptional and post-transcriptional levels.The mechanism of ferritin-mediated iron recycling is far from clarified,though nuclear receptor co-activator 4(NCOA4)was recently identified as a cargo receptor for ferritin-based lysosomal degradation.Cytosolic ferritins are heteropolymers assembled by H-and L-chains in different proportions.The mitochondrial ferritins are homopolymers and distributed in restricted tissues.They play protective roles in mitochondria where heme-and Fe/S-enzymes are synthesized and high levels of ROS are produced.Genetic ferritin disorders are mainly related to the L-chain mutations,which generally cause severe movement diseases.This review is focused on the biochemistry and function of mammalian intracellular ferritin as the major iron-storage and anti-oxidation protein.展开更多
Aging is a physiological process that leads to degeneration and functional decline of the brain.This is accompanied by intracellular peroxidation and neuronal apoptosis.Natural antioxidants possess a remarkable effect...Aging is a physiological process that leads to degeneration and functional decline of the brain.This is accompanied by intracellular peroxidation and neuronal apoptosis.Natural antioxidants possess a remarkable effect on attenuating the oxidative stress cascade and apoptosis of neurons;however,the challenge of using natural antioxidants for neuroprotection is fabricating a delivery system to overcome the blood-brain barrier(BBB)transport.Herein,we successfully created a stable delivery platform built on rigid ferritin nanocage loading natural lycopene molecules,crossing the BBB in quantity and being taken up in neurons.This nanoparticle worked on D-galactose-induced senescence via alleviating neuronal hyperoxidation injury and weakening neuronal apoptosis in PC12 and BV2 cells.More importantly,this natural delivery system possesses inherent biocompatibility and potential application in improving the bioavailability of bioactive edible compounds with low water solubility.This study demonstrated the effectiveness of natural antioxidant nanomedicines in maintaining the defenses of intracerebral peroxidation and improve degenerating neurons,providing the potential to combat further imbalances of neuronal microenvironment in aging neuropathy.展开更多
Objective:To investigate the diagnostic status and electrocardiographic correlates in patients with biochemical evidence of iron overload.Methods:We conducted a retrospective cohort study of patients in our hospital w...Objective:To investigate the diagnostic status and electrocardiographic correlates in patients with biochemical evidence of iron overload.Methods:We conducted a retrospective cohort study of patients in our hospital with ferritin levels exceeding 500 ng/mL between January 1,2011,and October 24,2022(corresponding to the pre-COVID-19 pandemic period in Beijing).Using ICD-10-CM coded medical records,we assessed the following:definitive diagnostic characterization(genetic or acquired),electrocardiographic(ECG)completion rates,and the prevalence of ECG abnormalities.Statistical analyses,encompassing chi-square tests and correlation studies,were performed using SPSS Statistics software(version 27.0).Results:Except for cases of malignancy,infectious diseases,hematological diseases,chronic diseases,for the unexplained diagnosis group found elevated ferritin during annual health checkup,there were 17 cases in the group with ferritin above 1,000 ng/ml and 36 cases in the group with ferritin ranging from 500 to 1,000 ng/ml,accounting for 23.2%and 25.8%of the entire ferritin analysis respectively,and the total proportion in the entire analysis was 24.0%.Among the cases indicating ferritin higher than 500ng/ml,24.0%of the cases were of unknown diagnosis.ECG acquisition rate for was 55.7%,with 24% demonstrating abnormalities,including atrial fibrillation,sinus tachycardia arrhythmia,atrioventricular block,prolonged QT interval,T-wave inversion,and ST-segment depression.Conclusion:The study revealed that the proportion of unexplained diagnoses of ferritin overload remains relatively high,and the analysis of the ECG is also insufficient.There is a need to enhance clinicians’awareness and attention to iron overload in both diagnosis and ECG analysis.展开更多
Accurately distinguishing between the endogenous formation and exogenous exposure of Fe-bearing particles(e.g.,magnetic Fe particles)within biological organisms is the prerequisite for scientifically evaluating their ...Accurately distinguishing between the endogenous formation and exogenous exposure of Fe-bearing particles(e.g.,magnetic Fe particles)within biological organisms is the prerequisite for scientifically evaluating their health risks.However,this remains a challenging task due to lacking the comprehensive understanding of the endogenous formation process of Fe-bearing particles.Here,we report the formation dynamics of Fe-bearing particles under conditions closely resembling actual physiological conditions,and compare the morphological and structural differences between endogenous and exogenous Fe-bearing particles.We find that Fe-bearing particles can indeed form under physiological conditions at 37℃.In this process,phosphate plays a crucial role in the oxidation and mineralization of iron ions.Moreover,endogenously formed Fe-bearing particles typically have a diameter of less than8 nm,and iron is the only metal element present.Therefore,we propose that Fe-bearing particles found in the body with a diameter larger than 8 nm are mainly derived from exogenous exposure.For Fe-bearing particles smaller than 8 nm,it is necessary to combine associated elements and crystal structure characteristics to distinguish between endogenous and exogenous sources.This study provides direct evidence from endogenous metabolism for tracing Fe-bearing particles,especially magnetic iron particles,within the human body.展开更多
This letter offered commentary on the recently published article by Wang et al that investigated the relationship between iron metabolism disorders and sepsis-associated liver injury(SALI).The original study identifie...This letter offered commentary on the recently published article by Wang et al that investigated the relationship between iron metabolism disorders and sepsis-associated liver injury(SALI).The original study identified serum iron and total iron-binding capacity as potential predictive markers of SALI,contributing important insights to critical care hepatology.In this correspondence several methodological considerations that may influence the interpretation and general-izability of the findings were discussed.These include the limitations of a single-center design,the lack of serial biomarker measurements,the omission of hepcidin(a central iron regulatory hormone)as a measured variable,and the exclusive reliance on biochemical criteria for diagnosing liver injury.The potential value of incorporating imaging modalities and additional iron-related markers such as ferritin and transferrin saturation were also highlighted.The aim was to reinforce the importance of a comprehensive approach to iron metabolism in sepsis and to suggest future directions for clinical research that may enhance the diagnostic and prognostic utility of iron-related biomarkers in SALI.展开更多
According to the conserved sequence of the ferritin gene, a homologous sequence was obtained from the EST database through a BLAST search against the GenBank database. This sequence was amplified with the method of RT...According to the conserved sequence of the ferritin gene, a homologous sequence was obtained from the EST database through a BLAST search against the GenBank database. This sequence was amplified with the method of RT-PCR, false sequencing was corrected, and full length eDNA of the ferritin subunit from the Chinese sturgeon was obtained. After being submitted to the GenBank database, the sequence accession number EU348782 was assigned. With the length of 896 bp, this eDNA includes entire coding regions of 53 lbp, which encodes 176 amino acids （aa）. The molecular weight was predicted to be 20339.9Mr and the theoretical isoelectric point 5.66. It shares 82.9% protein sequence homology with the ferritin of the Atlantic salmon. This gene is expressed in many organs of the Chinese sturgeon, for example, the liver, pancreas, muscle, brain, heart and gastric mucosa. The highest expression level was found in the pancreas and the heart, while the muscular tissue showed the lowest. Homology modeling was used to predict the 3-D structure of the protein, which included 5 alpha helices and 10 turns. The ferritin protein structure could be overlapped and showed high similarity with that of human, flog and bacteria. It was revealed that this kind of ferritin was highly conserved in structure and function.展开更多
[Objective] The aim of the present study was to investigate the characteristics of calcium （Ca）, magnesium （Mg） and iron （Fe） subcellular distributions in oilseed rape （Brassica napus L.） leaves during cold ac...[Objective] The aim of the present study was to investigate the characteristics of calcium （Ca）, magnesium （Mg） and iron （Fe） subcellular distributions in oilseed rape （Brassica napus L.） leaves during cold acclimatization. [Method] A field experiment was conducted at two contrasting environments with three replicates and included a freezing sensitive variety （cv. Zhongshuang No. 11, ZS） and a freezing tolerant variety （cv. Ganyouza No. 1, GY）. [Result] The concentrations of Ca, Mg and Fe were significantly increased in plants roots, and the concentrations of Ca and Mg were significantly decreased but the Fe concentration was significantly increased in plants shoots. In leaves, the Ca concentration stored in soluble fraction was significantly increased and the Ca concentration of organelle-contained fraction and cell wall-associated fraction were significantly decreased with experiment time. The Mg concentrations stored in soluble fraction, organelle-contained fraction and cell wall-associated fraction were decreased with time. In contrary, the Fe concentration stored in soluble fraction, organelle-contained fraction and cell wall associated-fraction was significantly increased with time. Meanwhile, the changes of these measures of ZS were much higher than those of GY during cold acclimatization, which might be due to the GY is a freezing tolerant variety but ZS is not. [Conclusion] These results suggested that increasing the concentrations of Ca, Mg and Fe in plants shoots might increase the cold resistance of oilseed rape.展开更多
基金Support by the German Research Foundationthe Open Access Publication Funds of the Gottingen University
文摘AIM To studied iron metabolism in liver, spleen, and serum after acute liver-damage, in relation to surrogate markers for liver-damage and repair.METHODS Rats received intraperitoneal injection of the hepatotoxin thioacetamide(TAA), and were sacrificed regularly between 1 and 96 h thereafter. Serum levels of transaminases and iron were measured using conventional laboratory assays. Liver tissue was used for conventional histology, immunohistology, and iron staining. The expression of acute-phase cytokines, ferritin light chain(FTL), and ferritin heavy chain(FTH)was investigated in the liver by q RT-PCR. Western blotting was used to investigate FTL and FTH in liver tissue and serum. Liver and spleen tissue was also used to determine iron concentrations.RESULTS After a short initial decrease, iron serum concentrations increased in parallel with serum transaminase(aspartate aminotransferase and alanine aminotransferase) levels, which reached a maximum at 48 h, and decreased thereafter. Similarly, after 48 h a significant increase in FTL, and after 72 h in FTH was detected in serum. While earliest morphological signs of inflammation in liver were visible after 6 h, increased expression of the two acute-phase cytokines IFN-γ(1 h) and IL-1β(3 h) was detectable earlier, with maximum values after 12-24 h. Iron concentrations in liver tissue increased steadily between 1 h and 48 h, and remained high at 96 h. In contrast, spleen iron concentrations remained unchanged until 48 h, and increased mildly thereafter(96 h). Although tissue iron staining was negative, hepatic FTL and FTH protein levels were strongly elevated. Our results reveal effects on hepatic iron concentrations after direct liver injury by TAA. The increase of liver iron concentrations may be due to the uptake of a significant proportion of the metal by healthy hepatocytes, and only to a minor extent by macrophages, as spleen iron concentrations do not increase in parallel. The temporary increase of iron, FTH and transaminases in serum is obviously due to their release by damaged hepatocytes.CONCLUSION Increased liver iron levels may be the consequence of hepatocyte damage. Iron released into serum by damaged hepatocytes is obviously transported back and stored via ferritins.
基金Sanming Project of Medicine in Shenzhen(SZSM201612031)the National Natural Science Foundation of China(81722024,81772736,81571728)+3 种基金Chinese Academy of Sciences(YJKYYQ20180048)the Basic Research Foundation for Shenzhen’s Science and Technology(20190726095103499)the National Key Research and Development Program of China(2017YFA0205501,2017YFA0205503)the Youth Innovation Promotion Association(2014078).
文摘Ferritin,an iron-storage protein,regulates cellular iron metabolism and oxidative stress.The ferritin structure is characterized as a spherical cage,inside which large amounts of iron are deposited in a safe,compact and bioavailable form.All ferritins readily catalyze Fe(II)oxidation by peroxides at the ferroxidase center to prevent free Fe(II)from participating in oxygen free radical formation via Fenton chemistry.Thus,ferritin is generally recognized as a cytoprotective stratagem against intracellular oxidative damage.The expression of cytosolic ferritins is usually regulated by iron status and oxidative stress at both the transcriptional and post-transcriptional levels.The mechanism of ferritin-mediated iron recycling is far from clarified,though nuclear receptor co-activator 4(NCOA4)was recently identified as a cargo receptor for ferritin-based lysosomal degradation.Cytosolic ferritins are heteropolymers assembled by H-and L-chains in different proportions.The mitochondrial ferritins are homopolymers and distributed in restricted tissues.They play protective roles in mitochondria where heme-and Fe/S-enzymes are synthesized and high levels of ROS are produced.Genetic ferritin disorders are mainly related to the L-chain mutations,which generally cause severe movement diseases.This review is focused on the biochemistry and function of mammalian intracellular ferritin as the major iron-storage and anti-oxidation protein.
基金financially supported by the National Natural Science Foundation of China(31730069)Graduate Innovation Fund of Dalian Polytechnic University。
文摘Aging is a physiological process that leads to degeneration and functional decline of the brain.This is accompanied by intracellular peroxidation and neuronal apoptosis.Natural antioxidants possess a remarkable effect on attenuating the oxidative stress cascade and apoptosis of neurons;however,the challenge of using natural antioxidants for neuroprotection is fabricating a delivery system to overcome the blood-brain barrier(BBB)transport.Herein,we successfully created a stable delivery platform built on rigid ferritin nanocage loading natural lycopene molecules,crossing the BBB in quantity and being taken up in neurons.This nanoparticle worked on D-galactose-induced senescence via alleviating neuronal hyperoxidation injury and weakening neuronal apoptosis in PC12 and BV2 cells.More importantly,this natural delivery system possesses inherent biocompatibility and potential application in improving the bioavailability of bioactive edible compounds with low water solubility.This study demonstrated the effectiveness of natural antioxidant nanomedicines in maintaining the defenses of intracerebral peroxidation and improve degenerating neurons,providing the potential to combat further imbalances of neuronal microenvironment in aging neuropathy.
文摘Objective:To investigate the diagnostic status and electrocardiographic correlates in patients with biochemical evidence of iron overload.Methods:We conducted a retrospective cohort study of patients in our hospital with ferritin levels exceeding 500 ng/mL between January 1,2011,and October 24,2022(corresponding to the pre-COVID-19 pandemic period in Beijing).Using ICD-10-CM coded medical records,we assessed the following:definitive diagnostic characterization(genetic or acquired),electrocardiographic(ECG)completion rates,and the prevalence of ECG abnormalities.Statistical analyses,encompassing chi-square tests and correlation studies,were performed using SPSS Statistics software(version 27.0).Results:Except for cases of malignancy,infectious diseases,hematological diseases,chronic diseases,for the unexplained diagnosis group found elevated ferritin during annual health checkup,there were 17 cases in the group with ferritin above 1,000 ng/ml and 36 cases in the group with ferritin ranging from 500 to 1,000 ng/ml,accounting for 23.2%and 25.8%of the entire ferritin analysis respectively,and the total proportion in the entire analysis was 24.0%.Among the cases indicating ferritin higher than 500ng/ml,24.0%of the cases were of unknown diagnosis.ECG acquisition rate for was 55.7%,with 24% demonstrating abnormalities,including atrial fibrillation,sinus tachycardia arrhythmia,atrioventricular block,prolonged QT interval,T-wave inversion,and ST-segment depression.Conclusion:The study revealed that the proportion of unexplained diagnoses of ferritin overload remains relatively high,and the analysis of the ECG is also insufficient.There is a need to enhance clinicians’awareness and attention to iron overload in both diagnosis and ECG analysis.
基金supported by the National Natural Science Foundation of China(Nos.22222610,22376202,and 22193051)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB0750100)+1 种基金Chinese Academy of Sciences Project for Young in Basic Research(No.YSBR-086)the National Key R&D Program of China(Nos.2023YFF0614200 and 2023YFC3708301)。
文摘Accurately distinguishing between the endogenous formation and exogenous exposure of Fe-bearing particles(e.g.,magnetic Fe particles)within biological organisms is the prerequisite for scientifically evaluating their health risks.However,this remains a challenging task due to lacking the comprehensive understanding of the endogenous formation process of Fe-bearing particles.Here,we report the formation dynamics of Fe-bearing particles under conditions closely resembling actual physiological conditions,and compare the morphological and structural differences between endogenous and exogenous Fe-bearing particles.We find that Fe-bearing particles can indeed form under physiological conditions at 37℃.In this process,phosphate plays a crucial role in the oxidation and mineralization of iron ions.Moreover,endogenously formed Fe-bearing particles typically have a diameter of less than8 nm,and iron is the only metal element present.Therefore,we propose that Fe-bearing particles found in the body with a diameter larger than 8 nm are mainly derived from exogenous exposure.For Fe-bearing particles smaller than 8 nm,it is necessary to combine associated elements and crystal structure characteristics to distinguish between endogenous and exogenous sources.This study provides direct evidence from endogenous metabolism for tracing Fe-bearing particles,especially magnetic iron particles,within the human body.
文摘This letter offered commentary on the recently published article by Wang et al that investigated the relationship between iron metabolism disorders and sepsis-associated liver injury(SALI).The original study identified serum iron and total iron-binding capacity as potential predictive markers of SALI,contributing important insights to critical care hepatology.In this correspondence several methodological considerations that may influence the interpretation and general-izability of the findings were discussed.These include the limitations of a single-center design,the lack of serial biomarker measurements,the omission of hepcidin(a central iron regulatory hormone)as a measured variable,and the exclusive reliance on biochemical criteria for diagnosing liver injury.The potential value of incorporating imaging modalities and additional iron-related markers such as ferritin and transferrin saturation were also highlighted.The aim was to reinforce the importance of a comprehensive approach to iron metabolism in sepsis and to suggest future directions for clinical research that may enhance the diagnostic and prognostic utility of iron-related biomarkers in SALI.
文摘According to the conserved sequence of the ferritin gene, a homologous sequence was obtained from the EST database through a BLAST search against the GenBank database. This sequence was amplified with the method of RT-PCR, false sequencing was corrected, and full length eDNA of the ferritin subunit from the Chinese sturgeon was obtained. After being submitted to the GenBank database, the sequence accession number EU348782 was assigned. With the length of 896 bp, this eDNA includes entire coding regions of 53 lbp, which encodes 176 amino acids （aa）. The molecular weight was predicted to be 20339.9Mr and the theoretical isoelectric point 5.66. It shares 82.9% protein sequence homology with the ferritin of the Atlantic salmon. This gene is expressed in many organs of the Chinese sturgeon, for example, the liver, pancreas, muscle, brain, heart and gastric mucosa. The highest expression level was found in the pancreas and the heart, while the muscular tissue showed the lowest. Homology modeling was used to predict the 3-D structure of the protein, which included 5 alpha helices and 10 turns. The ferritin protein structure could be overlapped and showed high similarity with that of human, flog and bacteria. It was revealed that this kind of ferritin was highly conserved in structure and function.
基金Supported by the Special Funds of Public Welfare Institutes of China(1610172011016)the Special Funds for Public Welfare Industry(Agriculture)Study of China(200903003)~~
文摘[Objective] The aim of the present study was to investigate the characteristics of calcium （Ca）, magnesium （Mg） and iron （Fe） subcellular distributions in oilseed rape （Brassica napus L.） leaves during cold acclimatization. [Method] A field experiment was conducted at two contrasting environments with three replicates and included a freezing sensitive variety （cv. Zhongshuang No. 11, ZS） and a freezing tolerant variety （cv. Ganyouza No. 1, GY）. [Result] The concentrations of Ca, Mg and Fe were significantly increased in plants roots, and the concentrations of Ca and Mg were significantly decreased but the Fe concentration was significantly increased in plants shoots. In leaves, the Ca concentration stored in soluble fraction was significantly increased and the Ca concentration of organelle-contained fraction and cell wall-associated fraction were significantly decreased with experiment time. The Mg concentrations stored in soluble fraction, organelle-contained fraction and cell wall-associated fraction were decreased with time. In contrary, the Fe concentration stored in soluble fraction, organelle-contained fraction and cell wall associated-fraction was significantly increased with time. Meanwhile, the changes of these measures of ZS were much higher than those of GY during cold acclimatization, which might be due to the GY is a freezing tolerant variety but ZS is not. [Conclusion] These results suggested that increasing the concentrations of Ca, Mg and Fe in plants shoots might increase the cold resistance of oilseed rape.
