BACKGROUND Sepsis-associated liver injury(SALI)refers to secondary liver function impairment caused by sepsis,patients with SALI often have worse clinical outcomes.The early identification and assessment of the occurr...BACKGROUND Sepsis-associated liver injury(SALI)refers to secondary liver function impairment caused by sepsis,patients with SALI often have worse clinical outcomes.The early identification and assessment of the occurrence and progression of SALI are pressing issues that urgently need to be resolved.AIM To investigate the relationship between iron metabolism and SALI.METHODS In this prospective study,139 patients were recruited,with 53 assigned to the SALI group.The relationships between SALI and various iron metabolism-related biomarkers were examined.These biomarkers included serum iron(SI),total iron-binding capacity(TIBC),serum ferritin,transferrin,and transferrin saturation.To identify independent risk factors for SALI,both univariate and multivariate logistic regression analyses were performed.Additionally,receiver operating characteristic curve analysis was utilized to assess the predictive value of these biomarkers for the occurrence of SALI.RESULTS There were no statistically significant differences in age,sex,body mass index,Sequential Organ Failure Assessment scores(excluding liver function),or APACHE II scores between the two groups of patients.Compared with the sepsis group,the SALI group presented significantly higher SI(P<0.001),TIBC(P<0.001),serum ferritin(P=0.001),transferrin(P=0.005),and transferrin saturation levels(P<0.001).Multivariate logistic regression analysis revealed that SI(odds ratio=1.24,95%confidence interval:1.11-1.40,P<0.001)and TIBC levels(odds ratio=1.13,95%confidence interval:1.05-1.21,P<0.001)were independent predictors of SALI.Receiver operating characteristic curve analysis revealed that SI and TIBC had areas under the curve of 0.816 and 0.757,respectively,indicating moderate predictive accuracy for SALI.CONCLUSION Iron metabolism disorders are closely associated with the development of SALI,and SI and TIBC may serve as potential predictive biomarkers.The combined use of SI and TIBC has superior diagnostic efficacy for SALI.These findings provide valuable insights for the early identification and management of SALI among patients with sepsis.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
BACKGROUND:Iron metabolism dyshomeostasis is associated with ferroptosis and ischemiareperfusion injury.We aim to investigate post-cardiac arrest changes in plasma iron metabolism-related parameters and their prognost...BACKGROUND:Iron metabolism dyshomeostasis is associated with ferroptosis and ischemiareperfusion injury.We aim to investigate post-cardiac arrest changes in plasma iron metabolism-related parameters and their prognostic value for 28-day neurological outcomes.METHODS:In this prospective observational cohort study,plasma iron metabolism-related parameters(iron,ferritin,hepcidin,soluble transferrin receptor[sTfR],total iron binding capacity[TIBC],and transferrin saturation),interleukin-6,and neuron-specific enolase(NSE)were assessed in 120 patients after restoration of spontaneous circulation(ROSC)on days 1 and 3 of intensive care unit(ICU)admission and in 40 healthy controls.The primary outcome was poor 28-day neurological prognosis.RESULTS:Compared to controls,post-ROSC patients exhibited significant plasma iron metabolism disturbances,including decreased iron,TIBC,transferrin saturation,with elevated hepcidin,ferritin,sTfR,interleukin-6,and NSE on day 1 after ICU admission(P<0.05 for all).On day 28 post-ROSC,patients with poor neurological outcomes(71/120)presented more pronounced alterations than those with good neurological outcomes.Binary logistic analysis revealed that a plasma iron concentration≤11.2μmol/L(odds ratio[OR]0.607,95% confidence interval[CI]0.455-0.808)and an NSE concentration≥20.5 ng/mL(OR 1.020,95%CI 1.005-1.035)on day 1 of ICU admission were associated with 28-day poor neurological outcomes.The plasma iron-NSE combination showed better predictive performance(area under the curve=0.935,sensitivity 89.8%,specificity 84.5%).CONCLUSION:Early post-ROSC plasma iron metabolism disturbances combined with NSE elevation were associated with the 28-day neurological prognosis,suggesting the therapeutic potential of targeting the iron metabolism pathway.展开更多
Cancer cells undergo substantial metabolic alterations to sustain increased energy supply and uncontrolled proliferation.As an essential trace element,iron is vital for many biological processes.Evidence has revealed ...Cancer cells undergo substantial metabolic alterations to sustain increased energy supply and uncontrolled proliferation.As an essential trace element,iron is vital for many biological processes.Evidence has revealed that cancer cells deploy various mechanisms to elevate the cellular iron concentration to accelerate proliferation.Ferroptosis,a form of cell death caused by iron-catalyzed excessive peroxidation of polyunsaturated fatty acids(PUFAs),is a promising therapeutic target for therapyresistant cancers.Previous studies have reported that long noncoding RNA(lncRNA)is a group of critical regulators involved in modulating cell metabolism,proliferation,apoptosis,and ferroptosis.In this review,we summarize the associations among iron metabolism,ferroptosis,and ferroptosis-related lncRNA in tumorigenesis.This information will help deepen understanding of the role of lncRNA in iron metabolism and raise the possibility of targeting lncRNA and ferroptosis in cancer combination therapy.展开更多
The brain injury associated with neonatal hypoxia ischemia（HI）is a major contributor to neonatal mortality and neurodevelopment retardation.Approximately 30-40%of infants with brain injury will die and 20-40%of surv...The brain injury associated with neonatal hypoxia ischemia（HI）is a major contributor to neonatal mortality and neurodevelopment retardation.Approximately 30-40%of infants with brain injury will die and 20-40%of survivors will develop significant neurological disorders and lifelong disability.展开更多
BACKGROUND:This study aims to evaluate the eff ect of continuous renal replacement therapy(CRRT)on inflammation-related anemia,iron metabolism,and the prognosis in sepsis patients with acute kidney injury(AKI).METHODS...BACKGROUND:This study aims to evaluate the eff ect of continuous renal replacement therapy(CRRT)on inflammation-related anemia,iron metabolism,and the prognosis in sepsis patients with acute kidney injury(AKI).METHODS:Sepsis patients with AKI were prospectively enrolled and randomized into the CRRT and control groups.The clinical and laboratory data on days 1,3 and 7 after intensive care unit(ICU)admission were collected.The serum interleukin(IL)-6,hepcidin,erythropoietin,ferritin,and soluble transferrin receptor(sTfR)were determined by enzyme-linked immunosorbent assay.The Sequential Organ Failure Assessment(SOFA)score and 28-day mortality were recorded.Data were analyzed using Pearson’s Chi-square test or Fisher’s exact test(categorical variables),and Mann-Whitney U-test or t-test(continuous variables).RESULTS:The hemoglobin and serum erythropoietin levels did not signifi cantly diff er between the CRRT and control groups though gradually decreased within the first week of ICU admission.On days 3 and 7,the serum IL-6,hepcidin,ferritin,and red blood cell distribution width significantly decreased in the CRRT group compared to the control group(all P<0.05).On day 7,the serum iron was significantly elevated in the CRRT group compared to the control group(P<0.05).However,the serum sTfR did not signifi cantly diff er between the groups over time.In addition,the SOFA scores were signifi cantly lower in the CRRT group compared to the control group on day 7.The 28-day mortality did not signifi cantly diff er between the control and CRRT groups(38.0%vs.28.2%,P=0.332).CONCLUSION:CRRT might have beneficial effects on the improvement in inflammationrelated iron metabolism and disease severity during the fi rst week of ICU admission but not anemia and 28-day mortality in sepsis patients with AKI.展开更多
Clinical staging,Gleason score,and prostate-specific antigen(PSA)have been accepted as factors for evaluating the prognosis of prostate cancer(PCa).With the in-depth study of iron metabolism and the development of mul...Clinical staging,Gleason score,and prostate-specific antigen(PSA)have been accepted as factors for evaluating the prognosis of prostate cancer(PCa).With the in-depth study of iron metabolism and the development of multiparametric magnetic resonance imaging technology,we used q-Dixon magnetic resonance imaging(MRI)to measure the iron content of the PCa patients'lesions,and used enzyme-linked immunosorbent assay(ELISA)to measure the iron metabolism indicators in the patients'serum samples,combined with the patients'postoperative clinical data for analysis.We found that the serum indexes were correlated with the T2 star values,International Society of Urological Pathology(ISUP)grade,and pathological classification in PCa patients(all P<O.001)but not in benign prostatic hyperplasia(BPH)patients(all P>O.05).The utilization of q-Dixon-based MRI and serum indexes allows the noninvasive measurement of iron content in prostate lesions and the assessment of differential iron metabolism between PCa and BPH,which may be helpful for evaluating the prognosis of PCa.展开更多
Summary： The aim of this study was to investigate the changes of iron levels and hepatic regulatory molecules expression involved in iron metabolism in non-diabetic obese/type 2 diabetic rat models. Male Wistar rats ...Summary： The aim of this study was to investigate the changes of iron levels and hepatic regulatory molecules expression involved in iron metabolism in non-diabetic obese/type 2 diabetic rat models. Male Wistar rats were divided into 3 groups： control group, non-diabetic obese group and type 2 dia- betic group （n=20 each）. The rats were evaluated physiologically and biochemically. The hepatic histo- pathological changes were observed using haematoxylin and eosin （HE） staining. The mRNA expres- sion patterns of hepcidin, interleukin-6 （IL-6）, hypoxia-inducible factor （HIF） and ferroportin （Fpn） in the rat liver in control group, non-diabetic obese group and type 2 diabetic group were analyzed by real-time RT-PCR. The protein expression patterns of hepcidin in liver of each group were further ana- lyzed by immunohistochemistry and Western blotting. As compared with control group, the ferritin in non-diabetic obese group and type 2 diabetic group was increased significantly （P〈0.001）. However, there was no significant difference in soluble transferring receptor （sTfR）：ferritin ratio among the three groups （P〉0.05）. The real-time RT-PCR, immunohistochemistry and Western blotting results all re- vealed that the expression levels of hepcidin in non-diabetic obese group and type 2 diabetic group were elevated significantly as compared with those in control group （P〈0.001）. The expression levels of hep- cidin mRNA between non-diabetic obese group and type 2 diabetic group showed no significant differ- ence （P〉0.05）. However, the protein expression levels of hepcidin in type 2 diabetic group were sig- nificantly higher than those in non-diabetic obese group （P〈0.05）. Compared to control group, the ex- pression levels of IL-6 mRNA in non-diabetic obese group and type 2 diabetic group were increased significantly and the expression levels ofFpn mRNA decreased （P〈0.05）. However, the expression lev- els ofHIF mRNA had no significant difference among three groups. It is suggested that iron metabolism is substantially disturbed in non-diabetic obese and type 2 diabetic rats probably by the abnormal ex- pression of hepcidin in chronic inflammatory status. The increased hepcidin may restrain the iron re- lease from the cells by affecting the expression of Fpn, which probably associates with the development of diabetic complication.展开更多
[Objectives]This study was conducted to observe the effect of Lujingyiqishengxue Pill on iron metabolism in rats with iron deficiency anemia. [Methods] The iron-deficiency anemia rat model was established by feeding l...[Objectives]This study was conducted to observe the effect of Lujingyiqishengxue Pill on iron metabolism in rats with iron deficiency anemia. [Methods] The iron-deficiency anemia rat model was established by feeding low-iron diet. Meanwhile, the rats were given oral gavage of ferrous succinate(0.036 g/kg, positive drug group) and Lujingyiqishengxue Pill(4.4, 2.2, 1.1 g/kg, high, middle and low dose groups), once daily for 42 consecutive days. The body weight of the rats was observed every week, and the peripheral blood[red blood cells(RBC), hemoglobin(HGB), and hematocrit(HCT)]and the iron contents in tissues(the liver, spleen, small intestine, kidney) of the rats were detected after modeling;and serum iron(SI), serum total iron binding capacity(TIBC), transferrin saturation(TSAT), serum ferritin(SF) and serum transferrin receptor 1(TFR1) and other iron metabolism indexes were determined. [Results] Compared with the model group, the high-dose Lujingyiqishengxue Pill significantly reversed the peripheral blood(HGB, HCT) and iron contents of various tissues(the liver, spleen, small intestine, kidney) in rats(P<0.01), and significantly increased SI, TSAT, SF(P<0.01), while the contents of TIBC and TFR1 were significantly decreased(P<0.01). [Conclusions] Lujingyiqishengxue Pill can significantly improve anemia and regulate iron metabolism in rats with iron-deficiency anemia, which provides a pharmacological reference for the clinical application of Lujingyiqishengxue Pill.展开更多
Anxiety disorder is one of the most common emotional disorders,but its pathogenesis re-mains unclear.Research has shown that iron deficiency is more common in people with emotional disorders and that these disorders c...Anxiety disorder is one of the most common emotional disorders,but its pathogenesis re-mains unclear.Research has shown that iron deficiency is more common in people with emotional disorders and that these disorders can improve after taking iron supple-ments.Many factors can cause anxiety disorders,includ-ing external stress,genetic factors,impaired neurodevel-opment,and abnormal monoamine metabolism.Studies have shown that abnormal monoamine metabolism and impaired neurodevelopment can contribute to the severity of emotional disorders.The synthesis of serotonin(5-HT)and dopamine(DA)require iron as a cofactor in the syn-thesis of monoamine metabolism,and the release of epi-nephrine(E)was potentially associated with labile iron in plasma.At the same time,iron is also directly involved in myelin synthesis as a cofactor in neural development.Therefore,iron maybe involved some of the main causes of the onset of anxiety disorders.展开更多
Diabetic osteoporosis(DOP)is a common complication in diabetes,driven by hyperglycemia-induced metabolic disturbances,chronic inflammation,and oxi-dative stress.This review describes the critical role of iron metaboli...Diabetic osteoporosis(DOP)is a common complication in diabetes,driven by hyperglycemia-induced metabolic disturbances,chronic inflammation,and oxi-dative stress.This review describes the critical role of iron metabolism dysregu-lation in DOP pathogenesis,focusing on ferroptosis,a novel iron-dependent cell death pathway characterized by lipid peroxidation and reactive oxygen species(ROS)overproduction.Diabetic conditions exacerbate iron overload,impairing osteoblast function and enhancing osteoclast activity,while triggering ferroptosis in bone cells.Ferroptosis not only accelerates osteoblast apoptosis but also amplifies osteoclast-mediated bone resorption,synergistically promoting bone loss.Furthermore,chronic inflammation and oxidative stress disrupt the balance between bone formation and resorption,with elevated pro-inflammatory cyto-kines(e.g.,tumor necrosis factor-α,interleukin-6)and ROS exacerbating cellular dysfunction.Therapeutic strategies targeting iron metabolism(e.g.,deferoxamine)and ferroptosis inhibition(e.g.,nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway activation,antioxidants like melatonin)demonstrate potential to mitigate DOP progression.Future research should prioritize personalized interventions,clinical trials of iron chelators and antioxidants,and mechanistic studies to refine therapeutic approaches.This review provides a comprehensive framework for understanding DOP pathogenesis and highlights innovative strategies to improve bone health in diabetic patients.展开更多
Both iron metabolism and ferroptosis(an iron-dependent form of programmed cell death)have been connected to the development and progression of many currently incurable non-communicable diseases,including Alzheimer'...Both iron metabolism and ferroptosis(an iron-dependent form of programmed cell death)have been connected to the development and progression of many currently incurable non-communicable diseases,including Alzheimer's disease,Parkinson's disease,multiple sclerosis,Huntington's disease,metabolic dysfunction-associated steatohepatitis,heart failure,and both treatment-relapsed and refractory cancers,such as pancreatic ductal adenocarcinoma and triple-negative breast cancer.Thus,understanding the relationship between iron and these diseases can pave the way for the development of novel therapeutic strategies.Here,we summarize the latest evidence supporting the pathological roles of dysregulated iron metabolism and ferroptosis in a wide range of preclinical animal models of these currently incurable non-communicable diseases.We also summarize the feasibility of targeting iron metabolism and ferroptosis for the prevention and treatment of iron-and ferroptosis-related diseases that currently have limited treatment options.In addition,we provide our perspectives on the challenges and promises regarding the translational potential of targeting dysregulated iron metabolism and ferroptosis to treat diseases,highlighting the future roadmap for developing iron-and ferroptosis-targeted therapeutics.展开更多
Colorectal cancer(CRC)considerably affects global health,and its progression is intricately tied to interactions within the tumormicroenvironment.This review focuses on the intricate crosstalk between metabolic reprog...Colorectal cancer(CRC)considerably affects global health,and its progression is intricately tied to interactions within the tumormicroenvironment.This review focuses on the intricate crosstalk between metabolic reprogramming in CRC cells and the tumor immune microenvironment(TIME),thereby emphasizing the dual functionality of metabolic pathways in tumor growth and immune regulation.Furthermore,the review delves into key metabolic changes,including alterations in glucose,lipid,iron,and ammonia metabolism,and their profound effects on the immune landscape of CRC.Enhanced glycolysis and lipid metabolism facilitate tumor survival and proliferation,while establishing an immunosuppressive TIME that hinders effective immune responses.Moreover,the roles of iron and ammonia metabolism in immune evasion and tumor progression were explored,and these metabolic pathways presented as promising targets to improve CRC therapy.By conducting a comprehensive analysis of recent studies,this review provides insights into potential therapeutic targets within these metabolic interactions,with the aim of enhancing the efficacy of existing treatments and devising novel strategies for combating CRC.展开更多
Background:Retinal diseases can lead to severe visual impairment and even blindness,but current treatments are limited.For precise targeted therapy,the pathophysiological mechanisms of the diseases still need to be fu...Background:Retinal diseases can lead to severe visual impairment and even blindness,but current treatments are limited.For precise targeted therapy,the pathophysiological mechanisms of the diseases still need to be further explored.Iron serves an essential role in many biological activities and helps maintain the function and morphology of the retina.The vision problems caused by retinal diseases are affecting more and more people,the study of iron metabolism in retinal diseases possesses great potential for clinical application.Main text:Iron maintains a dynamic balance in the retina but in excess is toxic to the retina.Iron overload can lead to various pathological changes in the retina through oxidative stress,inflammation,cell death,angiogenesis and other pathways.It is therefore involved in the progression of retinal diseases such as age-related macular degeneration,glaucoma,diabetic retinopathy,retinitis pigmentosa,and hereditary iron overload.In recent years,iron chelators have been shown to be effective in the treatment of retinal diseases,but the exact mechanism is not yet fully understood.This question prompted further investigation into the specific mechanisms by which iron metabolism is involved in retinal disease.Conclusions:This review summarizes iron metabolism processes in the retina and mechanistic studies of iron metabolism in the progression of retinal disease.It also highlights the therapeutic potential of iron chelators in retinal diseases.展开更多
Iron is indispensable for the viablility of nearly all living organisms,and it is imperative for cells,tissues,and organisms to acquire this essential metal sufficiently and maintain its metabolic stability for surviv...Iron is indispensable for the viablility of nearly all living organisms,and it is imperative for cells,tissues,and organisms to acquire this essential metal sufficiently and maintain its metabolic stability for survival.Disruption of iron homeostasis can lead to the development of various diseases.There is a robust connection between iron metabolism and infection,immunity,inflammation,and aging,suggesting that disorders in iron metabolism may contribute to the pathogenesis of arthritis.Numerous studies have focused on the significant role of iron metabolism in the development of arthritis and its potential for targeted drug therapy.Targeting iron metabolism offers a promising approach for individualized treatment of arthritis.Therefore,this review aimed to investigate the mechanisms by which the body maintains iron metabolism and the impacts of iron and iron metabolism disorders on arthritis.Furthermore,this review aimed to identify potential therapeutic targets and active substances related to iron metabolism,which could provide promising research directions in this field.展开更多
Ferroptosis plays a critical pathophysiological role in several types of acute kidney injury(AKI).The development of nanomaterials targeting iron metabolism and ferroptosis is a promising approach for AKI treatment.He...Ferroptosis plays a critical pathophysiological role in several types of acute kidney injury(AKI).The development of nanomaterials targeting iron metabolism and ferroptosis is a promising approach for AKI treatment.Herein,we synthesized gallic acid-gallium polyvinyl pyrrolidone nanoparticles(GGP NPs)as a potential iron-scavenging agent because of their nearly ionic radius and chemical similarity with iron.The results indicated that GGP NPs accumulated in tubular epithelial cells and showed good biocompatibility.GGP NPs significantly inhibited cisplatin(CP)-induced ferroptosis in HK-2 cells by reducing the accumulation of intracellular free iron and mitochondrial dysfunction,and suppressing the perturbations of ferroptosis processes,including lipid peroxidation,nicotinamide adenine dinucleotide phosphate(NADPH)and glutathione(GSH)levels,glutathione peroxidase 4(GPX4)activity,and ferritinophagy.An in vivo study demonstrated that treatment with GGP NPs significantly ameliorated the renal tubular injury and mitochondrial damage induced by CP treatment or ischemia-reperfusion injury.Our study suggests that GGP NPs may be an effective and promising candidate for AKI treatment and enable potential clinical translation.展开更多
Type 2 diabetes(T2D)is a metabolic disorder with high prevalence and severe complications that has recently been indicated to be treatable by a combined static magnetic field(SMF)and electric field.We systematically c...Type 2 diabetes(T2D)is a metabolic disorder with high prevalence and severe complications that has recently been indicated to be treatable by a combined static magnetic field(SMF)and electric field.We systematically compared four types of SMFs and found that a downward SMF of100 mT could effectively reduce the development of hyperglycemia,fatty liver,weight gain,and tissue injury in high-fat-diet(HFD)/streptozocin-induced T2D mice,but not the upward SMF.The downward SMF markedly restored the Bacteroidetes population and reversed the iron complex outer membrane receptor gene reduction in the mice gut microbiota,and reduced iron deposition in the pancreas.SMF also reduced the labile iron and reactive oxygen species level in pancreatic Min6 cells in vitro and prevented palmitate-induced Min6 cell number reduction.Therefore,this simple SMF setting could partially prevent HFD-induced T2D development and ameliorate related symptoms,which could provide a low-cost and non-invasive physical method to prevent and/or treat T2D in the future.展开更多
Beyond its core role in iron metabolism,erythroferrone(ERFE)has emerged as a key player with far-reaching implications in various hematologic disorders.Its regulatory effect on hepcidin underlines its significance in ...Beyond its core role in iron metabolism,erythroferrone(ERFE)has emerged as a key player with far-reaching implications in various hematologic disorders.Its regulatory effect on hepcidin underlines its significance in conditions characterized by disrupted iron homeostasis.Inβ-thalassemia and myelodysplastic syndromes,its dysregulation intricately contributes to the clinical challenges of anemia and iron overload which highlights its potential as a therapeutic target.In anemia of chronic disease and iron deficiency anemia,ERFE presents a unique profile.In chronic kidney disease(CKD),the intricate interplay between ERFE,erythropoietin,and hepcidin undergoes dysregulation,contributing to the complex iron imbalance characteristic of this condition.Recent research suggests that ERFE plays a multifaceted role in restoring iron balance in CKD,beyond simply suppressing hepcidin production.The potential to modulate ERFE activity offers a novel approach to treating a spectrum of disorders associated with iron dysregulation.As our understanding of ERFE continues to evolve,it is poised to become a key focus in the development of targeted treatments,making it an exciting and dynamic area of ongoing research.Modulating ERFE activity presents a groundbreaking approach to treat iron dysregulation in conditions like iron deficiency anemia,thalassemia,and hemochromatosis.As new research unveils its intricate roles,ERFE has rapidly emerged as a key target for developing targeted therapies like ERFE agonists and antagonists.With promising studies underway,this dynamic field holds immense potential to improve patient outcomes,reduce complications,and offer personalized treatment options in hematology research.This comprehensive overview of ERFE’s role across various conditions underscores its pivotal function in iron metabolism and associated pathologies.展开更多
Iron(Fe)is a micronutrient for living organisms,and maintenance of Fe homeostasis is required for normal physiological functions.In this study,we report the function of a plasma membrane localized transporter(Polyol t...Iron(Fe)is a micronutrient for living organisms,and maintenance of Fe homeostasis is required for normal physiological functions.In this study,we report the function of a plasma membrane localized transporter(Polyol transporter 8,TaPLT8)in wheat,which is regarded as a novel regulator for Fe transport.TaPLT8 is specifically expressed in wheat roots and is induced by environmental Fe.Knockout of TaPLT8 increased Fe accumulation in roots but resulted in decreased Fe levels in shoots and grain.The change was caused by an altered tolerance or increased susceptibility to excessive environmental Fe in the vicinity of wheat roots,and inhibited root growth.Overexpression of TaPLT8A improved Fe transport from roots to shoots and grains,and increased grain Fe levels by up to 14.46%.Compared to wild type(WT)plants,the levels of Citrate and Fe levels in xylem sap were significantly decreased in taplt8 mutants but significantly increased in TaPLT8 OE lines.Transcriptome analysis of taplt8 mutants indicated that TaPLT8 affected citrate levels by influencing glycolysis and the citrate cycle pathway in roots,thus impacting Fe translocation.The findings demonstrated that TaPLT8 mediates Fe distribution in wheat roots and shoots,contributing to greater understanding of the contribution of TaPLT8 to Fe accumulation in grains.展开更多
Objectives To compare respiratory parameters of peripheral blood mononuclear cell mitochondria and iron metabolism indicators in patients with different NYHA functional classes of ischemic heart failure(HF).Methods Th...Objectives To compare respiratory parameters of peripheral blood mononuclear cell mitochondria and iron metabolism indicators in patients with different NYHA functional classes of ischemic heart failure(HF).Methods This single center, prospective, non-blinded study enrolled 20 patients with diagnosed chronic HF of ischemic genesis with reduced and mildly reduced left ventricle ejection fraction. The maximum oxygen consumption at the peak of the exercise test(VO2peak), iron metabolism parameters and respiratory activity of peripheral blood mononuclear cell mitochondria were assessed.Results Among the patients, a half of individuals were diagnosed with iron deficiency. Subgroups of patients with different HF severity did not significant differ in VO2peak(P=0.209), serum iron(P=0.468) and ferritin(P=0.235) levels. But there was a trend in increasing in these parameters with increasing NYHA HF functional class. Respiratory control coefficient(RC) in NADdependent and FAD-dependent mitochondrial oxidation were lower in patients with NYHA HF Ⅲ functional class compared to individuals with NYHA HF I functional class(P=0.028 and P=0.040, respectively). Serum iron(P=0.026), ferritin(P=0.045)levels, transferrin saturation(P=0.006) were negatively correlated with RC in NAD-dependent mitochondrial oxidation.Conclusions In aggravation of ischemic HF NYHA FC, there is a decrease in RC of PBMC mitochondria during the oxidation of NAD-dependent and FAD-dependent substrates. In the whole sample, patients with laboratory-confirmed iron deficiency accounted a half of the total number. Iron metabolism parameters had a paradoxical inverse relationship with the level of RC in PBMC mitochondria of patients with HF.展开更多
基金Supported by the National Science Foundation of Jiangsu Province,No.BK20221280the National Natural Science Foundation of China,No.82371336+2 种基金the Chinese Postdoctoral Science Foundation,No.2022M711426the Special Fund for Social Key Research and Development Plan of Yangzhou City,No.YZ2022097Yangzhou Municipal Science and Technology Bureau,No.YZ2024091 and No.YZ2022098.
文摘BACKGROUND Sepsis-associated liver injury(SALI)refers to secondary liver function impairment caused by sepsis,patients with SALI often have worse clinical outcomes.The early identification and assessment of the occurrence and progression of SALI are pressing issues that urgently need to be resolved.AIM To investigate the relationship between iron metabolism and SALI.METHODS In this prospective study,139 patients were recruited,with 53 assigned to the SALI group.The relationships between SALI and various iron metabolism-related biomarkers were examined.These biomarkers included serum iron(SI),total iron-binding capacity(TIBC),serum ferritin,transferrin,and transferrin saturation.To identify independent risk factors for SALI,both univariate and multivariate logistic regression analyses were performed.Additionally,receiver operating characteristic curve analysis was utilized to assess the predictive value of these biomarkers for the occurrence of SALI.RESULTS There were no statistically significant differences in age,sex,body mass index,Sequential Organ Failure Assessment scores(excluding liver function),or APACHE II scores between the two groups of patients.Compared with the sepsis group,the SALI group presented significantly higher SI(P<0.001),TIBC(P<0.001),serum ferritin(P=0.001),transferrin(P=0.005),and transferrin saturation levels(P<0.001).Multivariate logistic regression analysis revealed that SI(odds ratio=1.24,95%confidence interval:1.11-1.40,P<0.001)and TIBC levels(odds ratio=1.13,95%confidence interval:1.05-1.21,P<0.001)were independent predictors of SALI.Receiver operating characteristic curve analysis revealed that SI and TIBC had areas under the curve of 0.816 and 0.757,respectively,indicating moderate predictive accuracy for SALI.CONCLUSION Iron metabolism disorders are closely associated with the development of SALI,and SI and TIBC may serve as potential predictive biomarkers.The combined use of SI and TIBC has superior diagnostic efficacy for SALI.These findings provide valuable insights for the early identification and management of SALI among patients with sepsis.
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.
基金funded by the Shenzhen Key Medical Discipline Construction Fund(SZXK046)the Shenzhen Science and Technology Program(JCYJ20230807112007014).
文摘BACKGROUND:Iron metabolism dyshomeostasis is associated with ferroptosis and ischemiareperfusion injury.We aim to investigate post-cardiac arrest changes in plasma iron metabolism-related parameters and their prognostic value for 28-day neurological outcomes.METHODS:In this prospective observational cohort study,plasma iron metabolism-related parameters(iron,ferritin,hepcidin,soluble transferrin receptor[sTfR],total iron binding capacity[TIBC],and transferrin saturation),interleukin-6,and neuron-specific enolase(NSE)were assessed in 120 patients after restoration of spontaneous circulation(ROSC)on days 1 and 3 of intensive care unit(ICU)admission and in 40 healthy controls.The primary outcome was poor 28-day neurological prognosis.RESULTS:Compared to controls,post-ROSC patients exhibited significant plasma iron metabolism disturbances,including decreased iron,TIBC,transferrin saturation,with elevated hepcidin,ferritin,sTfR,interleukin-6,and NSE on day 1 after ICU admission(P<0.05 for all).On day 28 post-ROSC,patients with poor neurological outcomes(71/120)presented more pronounced alterations than those with good neurological outcomes.Binary logistic analysis revealed that a plasma iron concentration≤11.2μmol/L(odds ratio[OR]0.607,95% confidence interval[CI]0.455-0.808)and an NSE concentration≥20.5 ng/mL(OR 1.020,95%CI 1.005-1.035)on day 1 of ICU admission were associated with 28-day poor neurological outcomes.The plasma iron-NSE combination showed better predictive performance(area under the curve=0.935,sensitivity 89.8%,specificity 84.5%).CONCLUSION:Early post-ROSC plasma iron metabolism disturbances combined with NSE elevation were associated with the 28-day neurological prognosis,suggesting the therapeutic potential of targeting the iron metabolism pathway.
基金supported by the National Key Research and Development Program of China(No.2021YFC2700903)the National Basic Research Program of China(No.2017YFA0105201)+3 种基金the National Natural Science Foundation of China(Nos.81672791 and 81872300)the Zhejiang Provincial Natural Science Foundation of China for Distinguished Young Scholars(No.LR18C060002)the Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China(No.LHDMY22H160006)the ZJU-QILU Joint Research Institute QILU Group.
文摘Cancer cells undergo substantial metabolic alterations to sustain increased energy supply and uncontrolled proliferation.As an essential trace element,iron is vital for many biological processes.Evidence has revealed that cancer cells deploy various mechanisms to elevate the cellular iron concentration to accelerate proliferation.Ferroptosis,a form of cell death caused by iron-catalyzed excessive peroxidation of polyunsaturated fatty acids(PUFAs),is a promising therapeutic target for therapyresistant cancers.Previous studies have reported that long noncoding RNA(lncRNA)is a group of critical regulators involved in modulating cell metabolism,proliferation,apoptosis,and ferroptosis.In this review,we summarize the associations among iron metabolism,ferroptosis,and ferroptosis-related lncRNA in tumorigenesis.This information will help deepen understanding of the role of lncRNA in iron metabolism and raise the possibility of targeting lncRNA and ferroptosis in cancer combination therapy.
基金supported in part by National Institutes of Health grants(HL60190,HL67841,and P01HL0101902)
文摘The brain injury associated with neonatal hypoxia ischemia（HI）is a major contributor to neonatal mortality and neurodevelopment retardation.Approximately 30-40%of infants with brain injury will die and 20-40%of survivors will develop significant neurological disorders and lifelong disability.
基金funded by the Shenzhen Key Medical Discipline Construction Fund(S ZXK046)the National Nature Science Foundation of China(81571869).
文摘BACKGROUND:This study aims to evaluate the eff ect of continuous renal replacement therapy(CRRT)on inflammation-related anemia,iron metabolism,and the prognosis in sepsis patients with acute kidney injury(AKI).METHODS:Sepsis patients with AKI were prospectively enrolled and randomized into the CRRT and control groups.The clinical and laboratory data on days 1,3 and 7 after intensive care unit(ICU)admission were collected.The serum interleukin(IL)-6,hepcidin,erythropoietin,ferritin,and soluble transferrin receptor(sTfR)were determined by enzyme-linked immunosorbent assay.The Sequential Organ Failure Assessment(SOFA)score and 28-day mortality were recorded.Data were analyzed using Pearson’s Chi-square test or Fisher’s exact test(categorical variables),and Mann-Whitney U-test or t-test(continuous variables).RESULTS:The hemoglobin and serum erythropoietin levels did not signifi cantly diff er between the CRRT and control groups though gradually decreased within the first week of ICU admission.On days 3 and 7,the serum IL-6,hepcidin,ferritin,and red blood cell distribution width significantly decreased in the CRRT group compared to the control group(all P<0.05).On day 7,the serum iron was significantly elevated in the CRRT group compared to the control group(P<0.05).However,the serum sTfR did not signifi cantly diff er between the groups over time.In addition,the SOFA scores were signifi cantly lower in the CRRT group compared to the control group on day 7.The 28-day mortality did not signifi cantly diff er between the control and CRRT groups(38.0%vs.28.2%,P=0.332).CONCLUSION:CRRT might have beneficial effects on the improvement in inflammationrelated iron metabolism and disease severity during the fi rst week of ICU admission but not anemia and 28-day mortality in sepsis patients with AKI.
基金supported by grants from the 201816^(th) Science and Technology Development Plan of Suzhou,Suzhou,China(No.SS201863).
文摘Clinical staging,Gleason score,and prostate-specific antigen(PSA)have been accepted as factors for evaluating the prognosis of prostate cancer(PCa).With the in-depth study of iron metabolism and the development of multiparametric magnetic resonance imaging technology,we used q-Dixon magnetic resonance imaging(MRI)to measure the iron content of the PCa patients'lesions,and used enzyme-linked immunosorbent assay(ELISA)to measure the iron metabolism indicators in the patients'serum samples,combined with the patients'postoperative clinical data for analysis.We found that the serum indexes were correlated with the T2 star values,International Society of Urological Pathology(ISUP)grade,and pathological classification in PCa patients(all P<O.001)but not in benign prostatic hyperplasia(BPH)patients(all P>O.05).The utilization of q-Dixon-based MRI and serum indexes allows the noninvasive measurement of iron content in prostate lesions and the assessment of differential iron metabolism between PCa and BPH,which may be helpful for evaluating the prognosis of PCa.
文摘Summary： The aim of this study was to investigate the changes of iron levels and hepatic regulatory molecules expression involved in iron metabolism in non-diabetic obese/type 2 diabetic rat models. Male Wistar rats were divided into 3 groups： control group, non-diabetic obese group and type 2 dia- betic group （n=20 each）. The rats were evaluated physiologically and biochemically. The hepatic histo- pathological changes were observed using haematoxylin and eosin （HE） staining. The mRNA expres- sion patterns of hepcidin, interleukin-6 （IL-6）, hypoxia-inducible factor （HIF） and ferroportin （Fpn） in the rat liver in control group, non-diabetic obese group and type 2 diabetic group were analyzed by real-time RT-PCR. The protein expression patterns of hepcidin in liver of each group were further ana- lyzed by immunohistochemistry and Western blotting. As compared with control group, the ferritin in non-diabetic obese group and type 2 diabetic group was increased significantly （P〈0.001）. However, there was no significant difference in soluble transferring receptor （sTfR）：ferritin ratio among the three groups （P〉0.05）. The real-time RT-PCR, immunohistochemistry and Western blotting results all re- vealed that the expression levels of hepcidin in non-diabetic obese group and type 2 diabetic group were elevated significantly as compared with those in control group （P〈0.001）. The expression levels of hep- cidin mRNA between non-diabetic obese group and type 2 diabetic group showed no significant differ- ence （P〉0.05）. However, the protein expression levels of hepcidin in type 2 diabetic group were sig- nificantly higher than those in non-diabetic obese group （P〈0.05）. Compared to control group, the ex- pression levels of IL-6 mRNA in non-diabetic obese group and type 2 diabetic group were increased significantly and the expression levels ofFpn mRNA decreased （P〈0.05）. However, the expression lev- els ofHIF mRNA had no significant difference among three groups. It is suggested that iron metabolism is substantially disturbed in non-diabetic obese and type 2 diabetic rats probably by the abnormal ex- pression of hepcidin in chronic inflammatory status. The increased hepcidin may restrain the iron re- lease from the cells by affecting the expression of Fpn, which probably associates with the development of diabetic complication.
基金Supported by Science and Technology Planning Project (ZKHT[2020]-18-4)。
文摘[Objectives]This study was conducted to observe the effect of Lujingyiqishengxue Pill on iron metabolism in rats with iron deficiency anemia. [Methods] The iron-deficiency anemia rat model was established by feeding low-iron diet. Meanwhile, the rats were given oral gavage of ferrous succinate(0.036 g/kg, positive drug group) and Lujingyiqishengxue Pill(4.4, 2.2, 1.1 g/kg, high, middle and low dose groups), once daily for 42 consecutive days. The body weight of the rats was observed every week, and the peripheral blood[red blood cells(RBC), hemoglobin(HGB), and hematocrit(HCT)]and the iron contents in tissues(the liver, spleen, small intestine, kidney) of the rats were detected after modeling;and serum iron(SI), serum total iron binding capacity(TIBC), transferrin saturation(TSAT), serum ferritin(SF) and serum transferrin receptor 1(TFR1) and other iron metabolism indexes were determined. [Results] Compared with the model group, the high-dose Lujingyiqishengxue Pill significantly reversed the peripheral blood(HGB, HCT) and iron contents of various tissues(the liver, spleen, small intestine, kidney) in rats(P<0.01), and significantly increased SI, TSAT, SF(P<0.01), while the contents of TIBC and TFR1 were significantly decreased(P<0.01). [Conclusions] Lujingyiqishengxue Pill can significantly improve anemia and regulate iron metabolism in rats with iron-deficiency anemia, which provides a pharmacological reference for the clinical application of Lujingyiqishengxue Pill.
文摘Anxiety disorder is one of the most common emotional disorders,but its pathogenesis re-mains unclear.Research has shown that iron deficiency is more common in people with emotional disorders and that these disorders can improve after taking iron supple-ments.Many factors can cause anxiety disorders,includ-ing external stress,genetic factors,impaired neurodevel-opment,and abnormal monoamine metabolism.Studies have shown that abnormal monoamine metabolism and impaired neurodevelopment can contribute to the severity of emotional disorders.The synthesis of serotonin(5-HT)and dopamine(DA)require iron as a cofactor in the syn-thesis of monoamine metabolism,and the release of epi-nephrine(E)was potentially associated with labile iron in plasma.At the same time,iron is also directly involved in myelin synthesis as a cofactor in neural development.Therefore,iron maybe involved some of the main causes of the onset of anxiety disorders.
基金Supported by Henan Province Key Research and Development Program,No.231111311000Henan Provincial Science and Technology Research Project,No.232102310411+2 种基金Henan Province Medical Science and Technology Key Project,No.LHGJ20220566 and No.LHGJ20240365Henan Province Medical Education Research Project,No.WJLX2023079Zhengzhou Medical and Health Technology Innovation Guidance Program,No.2024YLZDJH022.
文摘Diabetic osteoporosis(DOP)is a common complication in diabetes,driven by hyperglycemia-induced metabolic disturbances,chronic inflammation,and oxi-dative stress.This review describes the critical role of iron metabolism dysregu-lation in DOP pathogenesis,focusing on ferroptosis,a novel iron-dependent cell death pathway characterized by lipid peroxidation and reactive oxygen species(ROS)overproduction.Diabetic conditions exacerbate iron overload,impairing osteoblast function and enhancing osteoclast activity,while triggering ferroptosis in bone cells.Ferroptosis not only accelerates osteoblast apoptosis but also amplifies osteoclast-mediated bone resorption,synergistically promoting bone loss.Furthermore,chronic inflammation and oxidative stress disrupt the balance between bone formation and resorption,with elevated pro-inflammatory cyto-kines(e.g.,tumor necrosis factor-α,interleukin-6)and ROS exacerbating cellular dysfunction.Therapeutic strategies targeting iron metabolism(e.g.,deferoxamine)and ferroptosis inhibition(e.g.,nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway activation,antioxidants like melatonin)demonstrate potential to mitigate DOP progression.Future research should prioritize personalized interventions,clinical trials of iron chelators and antioxidants,and mechanistic studies to refine therapeutic approaches.This review provides a comprehensive framework for understanding DOP pathogenesis and highlights innovative strategies to improve bone health in diabetic patients.
基金supported by the National Natural Science Foundation of China(82471593 to J.M.32330047,31930057 to F.W.)。
文摘Both iron metabolism and ferroptosis(an iron-dependent form of programmed cell death)have been connected to the development and progression of many currently incurable non-communicable diseases,including Alzheimer's disease,Parkinson's disease,multiple sclerosis,Huntington's disease,metabolic dysfunction-associated steatohepatitis,heart failure,and both treatment-relapsed and refractory cancers,such as pancreatic ductal adenocarcinoma and triple-negative breast cancer.Thus,understanding the relationship between iron and these diseases can pave the way for the development of novel therapeutic strategies.Here,we summarize the latest evidence supporting the pathological roles of dysregulated iron metabolism and ferroptosis in a wide range of preclinical animal models of these currently incurable non-communicable diseases.We also summarize the feasibility of targeting iron metabolism and ferroptosis for the prevention and treatment of iron-and ferroptosis-related diseases that currently have limited treatment options.In addition,we provide our perspectives on the challenges and promises regarding the translational potential of targeting dysregulated iron metabolism and ferroptosis to treat diseases,highlighting the future roadmap for developing iron-and ferroptosis-targeted therapeutics.
文摘Colorectal cancer(CRC)considerably affects global health,and its progression is intricately tied to interactions within the tumormicroenvironment.This review focuses on the intricate crosstalk between metabolic reprogramming in CRC cells and the tumor immune microenvironment(TIME),thereby emphasizing the dual functionality of metabolic pathways in tumor growth and immune regulation.Furthermore,the review delves into key metabolic changes,including alterations in glucose,lipid,iron,and ammonia metabolism,and their profound effects on the immune landscape of CRC.Enhanced glycolysis and lipid metabolism facilitate tumor survival and proliferation,while establishing an immunosuppressive TIME that hinders effective immune responses.Moreover,the roles of iron and ammonia metabolism in immune evasion and tumor progression were explored,and these metabolic pathways presented as promising targets to improve CRC therapy.By conducting a comprehensive analysis of recent studies,this review provides insights into potential therapeutic targets within these metabolic interactions,with the aim of enhancing the efficacy of existing treatments and devising novel strategies for combating CRC.
文摘Background:Retinal diseases can lead to severe visual impairment and even blindness,but current treatments are limited.For precise targeted therapy,the pathophysiological mechanisms of the diseases still need to be further explored.Iron serves an essential role in many biological activities and helps maintain the function and morphology of the retina.The vision problems caused by retinal diseases are affecting more and more people,the study of iron metabolism in retinal diseases possesses great potential for clinical application.Main text:Iron maintains a dynamic balance in the retina but in excess is toxic to the retina.Iron overload can lead to various pathological changes in the retina through oxidative stress,inflammation,cell death,angiogenesis and other pathways.It is therefore involved in the progression of retinal diseases such as age-related macular degeneration,glaucoma,diabetic retinopathy,retinitis pigmentosa,and hereditary iron overload.In recent years,iron chelators have been shown to be effective in the treatment of retinal diseases,but the exact mechanism is not yet fully understood.This question prompted further investigation into the specific mechanisms by which iron metabolism is involved in retinal disease.Conclusions:This review summarizes iron metabolism processes in the retina and mechanistic studies of iron metabolism in the progression of retinal disease.It also highlights the therapeutic potential of iron chelators in retinal diseases.
基金supported by grants from the National Natural Science Foundation of China(Nos.82030003 and 82001726)the CAMS Innovation Fund for Medical Sciences(No.2019-I2M-5-066)the Shanghai Municipal Science and Technology Major Project(No.2023SHZDZX02).
文摘Iron is indispensable for the viablility of nearly all living organisms,and it is imperative for cells,tissues,and organisms to acquire this essential metal sufficiently and maintain its metabolic stability for survival.Disruption of iron homeostasis can lead to the development of various diseases.There is a robust connection between iron metabolism and infection,immunity,inflammation,and aging,suggesting that disorders in iron metabolism may contribute to the pathogenesis of arthritis.Numerous studies have focused on the significant role of iron metabolism in the development of arthritis and its potential for targeted drug therapy.Targeting iron metabolism offers a promising approach for individualized treatment of arthritis.Therefore,this review aimed to investigate the mechanisms by which the body maintains iron metabolism and the impacts of iron and iron metabolism disorders on arthritis.Furthermore,this review aimed to identify potential therapeutic targets and active substances related to iron metabolism,which could provide promising research directions in this field.
基金supported by grants from the National Key R&D Program of China(No.2018YFC2000400)Zhejiang Provincial Natural Science Foundation of China(No.LZ22H050001)+1 种基金the National Natural Science Foundation of China(Nos.81970573,81670651,and 82000637)Zhejiang provincial program for the Cultivation of High-level Innovative Health talents,and Medical Health Science and Technology Project of Zhejiang Provincial Health Commission(No.2020KY538).
文摘Ferroptosis plays a critical pathophysiological role in several types of acute kidney injury(AKI).The development of nanomaterials targeting iron metabolism and ferroptosis is a promising approach for AKI treatment.Herein,we synthesized gallic acid-gallium polyvinyl pyrrolidone nanoparticles(GGP NPs)as a potential iron-scavenging agent because of their nearly ionic radius and chemical similarity with iron.The results indicated that GGP NPs accumulated in tubular epithelial cells and showed good biocompatibility.GGP NPs significantly inhibited cisplatin(CP)-induced ferroptosis in HK-2 cells by reducing the accumulation of intracellular free iron and mitochondrial dysfunction,and suppressing the perturbations of ferroptosis processes,including lipid peroxidation,nicotinamide adenine dinucleotide phosphate(NADPH)and glutathione(GSH)levels,glutathione peroxidase 4(GPX4)activity,and ferritinophagy.An in vivo study demonstrated that treatment with GGP NPs significantly ameliorated the renal tubular injury and mitochondrial damage induced by CP treatment or ischemia-reperfusion injury.Our study suggests that GGP NPs may be an effective and promising candidate for AKI treatment and enable potential clinical translation.
基金This work was supported by the National Key R&D Program of China(grant 2016YFA0400900)the Chinese Academy of Sciences Hefei Institutes of Physical Science Director's Fund(YZJJ201704)the Chinese National Natural Science Foundations(grant31800051).We would like to thank Heye Health Technology for providing the magnetic plates for the alternating magnetic field in Figure 1B.A portion of this work was supported by the High Magnetic Field Laboratory of Anhui Province.The authors have a patent pending related to this work.
文摘Type 2 diabetes(T2D)is a metabolic disorder with high prevalence and severe complications that has recently been indicated to be treatable by a combined static magnetic field(SMF)and electric field.We systematically compared four types of SMFs and found that a downward SMF of100 mT could effectively reduce the development of hyperglycemia,fatty liver,weight gain,and tissue injury in high-fat-diet(HFD)/streptozocin-induced T2D mice,but not the upward SMF.The downward SMF markedly restored the Bacteroidetes population and reversed the iron complex outer membrane receptor gene reduction in the mice gut microbiota,and reduced iron deposition in the pancreas.SMF also reduced the labile iron and reactive oxygen species level in pancreatic Min6 cells in vitro and prevented palmitate-induced Min6 cell number reduction.Therefore,this simple SMF setting could partially prevent HFD-induced T2D development and ameliorate related symptoms,which could provide a low-cost and non-invasive physical method to prevent and/or treat T2D in the future.
文摘Beyond its core role in iron metabolism,erythroferrone(ERFE)has emerged as a key player with far-reaching implications in various hematologic disorders.Its regulatory effect on hepcidin underlines its significance in conditions characterized by disrupted iron homeostasis.Inβ-thalassemia and myelodysplastic syndromes,its dysregulation intricately contributes to the clinical challenges of anemia and iron overload which highlights its potential as a therapeutic target.In anemia of chronic disease and iron deficiency anemia,ERFE presents a unique profile.In chronic kidney disease(CKD),the intricate interplay between ERFE,erythropoietin,and hepcidin undergoes dysregulation,contributing to the complex iron imbalance characteristic of this condition.Recent research suggests that ERFE plays a multifaceted role in restoring iron balance in CKD,beyond simply suppressing hepcidin production.The potential to modulate ERFE activity offers a novel approach to treating a spectrum of disorders associated with iron dysregulation.As our understanding of ERFE continues to evolve,it is poised to become a key focus in the development of targeted treatments,making it an exciting and dynamic area of ongoing research.Modulating ERFE activity presents a groundbreaking approach to treat iron dysregulation in conditions like iron deficiency anemia,thalassemia,and hemochromatosis.As new research unveils its intricate roles,ERFE has rapidly emerged as a key target for developing targeted therapies like ERFE agonists and antagonists.With promising studies underway,this dynamic field holds immense potential to improve patient outcomes,reduce complications,and offer personalized treatment options in hematology research.This comprehensive overview of ERFE’s role across various conditions underscores its pivotal function in iron metabolism and associated pathologies.
基金supported by the National Key Research and Development Program of China(2023YFF1001500)Young Scientists Fund of the National Natural Science Foundation of China(32401811)+3 种基金Key Program of Sichuan Natural Science Foundation(2022NSFSC0015)local financial funds of the National Agricultural Science and Technology Center,Chengdu(NASC2024KR01)research start up fund of Chengdu Agricultural College(25BS02),Significant Science and Technology Project of China National Tobacco Corporation(110202101060(XJ-09))Natural Science Foundation of Sichuan Province(2024NSFSC1204).
文摘Iron(Fe)is a micronutrient for living organisms,and maintenance of Fe homeostasis is required for normal physiological functions.In this study,we report the function of a plasma membrane localized transporter(Polyol transporter 8,TaPLT8)in wheat,which is regarded as a novel regulator for Fe transport.TaPLT8 is specifically expressed in wheat roots and is induced by environmental Fe.Knockout of TaPLT8 increased Fe accumulation in roots but resulted in decreased Fe levels in shoots and grain.The change was caused by an altered tolerance or increased susceptibility to excessive environmental Fe in the vicinity of wheat roots,and inhibited root growth.Overexpression of TaPLT8A improved Fe transport from roots to shoots and grains,and increased grain Fe levels by up to 14.46%.Compared to wild type(WT)plants,the levels of Citrate and Fe levels in xylem sap were significantly decreased in taplt8 mutants but significantly increased in TaPLT8 OE lines.Transcriptome analysis of taplt8 mutants indicated that TaPLT8 affected citrate levels by influencing glycolysis and the citrate cycle pathway in roots,thus impacting Fe translocation.The findings demonstrated that TaPLT8 mediates Fe distribution in wheat roots and shoots,contributing to greater understanding of the contribution of TaPLT8 to Fe accumulation in grains.
基金supported by Russian Science Foundation,RSF 23-75-00009(part of the study corresponding to finding 1)Part of the study corresponding to finding 2 was carried out within the state assignment,FSR No.:122020300045-5(03.02.2022).
文摘Objectives To compare respiratory parameters of peripheral blood mononuclear cell mitochondria and iron metabolism indicators in patients with different NYHA functional classes of ischemic heart failure(HF).Methods This single center, prospective, non-blinded study enrolled 20 patients with diagnosed chronic HF of ischemic genesis with reduced and mildly reduced left ventricle ejection fraction. The maximum oxygen consumption at the peak of the exercise test(VO2peak), iron metabolism parameters and respiratory activity of peripheral blood mononuclear cell mitochondria were assessed.Results Among the patients, a half of individuals were diagnosed with iron deficiency. Subgroups of patients with different HF severity did not significant differ in VO2peak(P=0.209), serum iron(P=0.468) and ferritin(P=0.235) levels. But there was a trend in increasing in these parameters with increasing NYHA HF functional class. Respiratory control coefficient(RC) in NADdependent and FAD-dependent mitochondrial oxidation were lower in patients with NYHA HF Ⅲ functional class compared to individuals with NYHA HF I functional class(P=0.028 and P=0.040, respectively). Serum iron(P=0.026), ferritin(P=0.045)levels, transferrin saturation(P=0.006) were negatively correlated with RC in NAD-dependent mitochondrial oxidation.Conclusions In aggravation of ischemic HF NYHA FC, there is a decrease in RC of PBMC mitochondria during the oxidation of NAD-dependent and FAD-dependent substrates. In the whole sample, patients with laboratory-confirmed iron deficiency accounted a half of the total number. Iron metabolism parameters had a paradoxical inverse relationship with the level of RC in PBMC mitochondria of patients with HF.
