The impact of different iron metabolism processes(DIMP)on ovarian cancer remains unclear.In this study,we employed various gene chips and databases to investigate the role of DIMP in the initiation and development of ...The impact of different iron metabolism processes(DIMP)on ovarian cancer remains unclear.In this study,we employed various gene chips and databases to investigate the role of DIMP in the initiation and development of ovarian cancer.cBioPortal was used to determine mutations in DIMP-associated genes in ovarian cancer.Kaplan-Meier plotter was used to examine the influence of DIMP on the prognosis of ovarian cancer.By analyzing 1669 serous ovarian cancer cases,we identified a range of mutations in iron metabolism genes,notably in those coding for the transferrin receptor(19%),melanotransferrin(19%),and ceruloplasmin(10%)in the iron import process,and glucose-6-phosphate isomerase(9%),hepcidin antimicrobial peptide(9%),metal regulatory transcription factor 1(8%),and bone morphogenetic protein 6(8%)in the iron regulation process.Compared to the unaltered group,the group with gene alterations exhibited a higher tumor mutation burden count(43 vs.54)and more advanced histologic grade(78.19%vs.87.90%).Compared to the normal ovarian counterparts,a reduction in expression was observed in 9 out of the 14 genes involved in iron utilization and 4 out of the 5 genes involved in iron export in ovarian cancer;in contrast,an increase in expression was observed in 2 out of the 3 genes involved in iron storage in ovarian cancer.Furthermore,in cisplatin-resistant cells compared to cisplatin-sensitive ones,the expression of all genes in iron storage and 13 out of 14 genes in iron import was decreased,while that of 8 out of the 10 genes in iron utilization was increased.In addition,survival curve analysis indicated that a higher expression in the majority of genes in the iron import process(12/21),or a reduced expression in most genes in the iron export process(4/5)correlated with poor progression-free survival.Additionally,TGF-βcould regulate the expression of most iron metabolism-associated genes;particularly,expression of genes involved in the iron storage process(2/2)was inhibited after TGF-β1 or TGF-β2 treatment.In conclusion,DIMP plays multifaceted roles in the initiation,chemo-resistance,and prognosis of ovarian cancer.Therapeutically targeting DIMP may pave the way for more tailored treatment approaches for ovarian cancer.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
Introduction: Sickle cell disease is the most common genetic disease in the world, particularly in sub-Saharan Africa. It is a protean condition with multiple complications including disturbed iron metabolism. Objecti...Introduction: Sickle cell disease is the most common genetic disease in the world, particularly in sub-Saharan Africa. It is a protean condition with multiple complications including disturbed iron metabolism. Objectives: To determine the prevalence of iron metabolism abnormalities in children with homozygous sickle cell disease, to describe the epidemiological, clinical and paraclinical characteristics of children with these abnormalities and to identify associated factors. Patients and Methods: This was a cross-sectional analytical study conducted over 9 months in the mother-child consultation unit of the Brazzaville University Hospital, the National Reference Centre for Sickle Cell Disease and the paediatric department of the Blanche Gomes mother-child hospital. It concerned children aged between 3 months and 15 years followed up for homozygous sickle cell disease. The study was based on a haemogram, iron metabolism test, LDH, transaminases and CRP. Results: The overall prevalence of iron metabolism abnomalities was 40.7%. Of the 145 children included, 35.9% had iron overload and 4.8% iron deficiency. Iron overload was associated with infections, undernutrition, iron supplementation and number of blood transfusions. Iron deficiency was not significantly associated with any factor but recurrent infections were relatively more frequent. Conclusion: Abnormalities of iron metabolism in sickle cell patients are relatively frequent, which justifies monitoring during follow-up for early detection and better management. .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
Iron is essential for all organisms including microbial,cancer and human cells. More than a quarter of the human population is affected by abnormalities of iron metabolism, mainly from iron deficiency and iron overloa...Iron is essential for all organisms including microbial,cancer and human cells. More than a quarter of the human population is affected by abnormalities of iron metabolism, mainly from iron deficiency and iron overload. Iron also plays an important role in free radical pathology and oxidative damage which is observed in almost all major diseases, cancer and ageing. New developments include the complete treatment of iron overload and reduction of morbidity and mortality in thalassaemia using deferiprone and selected deferiprone/deferoxamine combinations and also the use of the maltol iron complex in the treatment of iron deficiency anaemia. There is also a prospect of using deferiprone as a universal antioxidant in non iron overloaded diseases such as neurodegenerative, cardiovascular, renal, infectious diseases and cancer. New regulatory molecules of iron metabolism such as endogenous and dietary chelating molecules, hepcidin, mitochondrial ferritin and their role in health and disease is under evaluation. Similarly, new mechanisms of iron deposition, removal, distribution and toxicity have been identified using new techniques such as magnetic resonance imaging increasing our understanding of iron metabolic processes and the targeted treatment of related diseases. The uniform distribution of iron in iron overload between organs and within each organ is no longer valid. Several other controversies such as the toxicity impact of non transferrin bound iron vs injected iron, the excess levels of iron in tissues causing toxicity and the role of chelation on iron absorption need further investigation. Commercial interests of pharmaceutical companies and connections to leading journals are playing a crucial role in shaping worldwide medical opinion on drug sales and use but also patients' therapeutic outcome and safety. Major controversies include the selection criteria and risk/benefit assessment in the use of deferasirox in thalassaemia and more so in idiopathic haemochromatosis, thalassaemia intermedia and ex-thalassaemia transplanted patients who are safely treated with venesection. Iron chelating drugs can override normal regulatory pathways, correct iron imbalance and minimise iron toxicity. The use of iron chelating drugs as main, alternative or adjuvant therapy is in progress in many conditions, especially those with non established or effective therapies.展开更多
AIM To investigate the relationship between levels of iron metabolism markers and hepatitis B virus(HBV)-related chronic liver diseases.METHODS This case-control study with 318 participants included 78 cases of chroni...AIM To investigate the relationship between levels of iron metabolism markers and hepatitis B virus(HBV)-related chronic liver diseases.METHODS This case-control study with 318 participants included 78 cases of chronic hepatitis B, 85 cases of HBV-related liver cirrhosis, 77 cases of HBV-related hepatocellular carcinoma, and 78 healthy controls. Markers of iron metabolism were detected in participants. Hematological and biochemical parameters and HBV-DNA were assessed. Child-Pugh grade and Barcelona Clinic Liver Cancer stage were determined for each hepatocellular carcinoma patient. Perls' staining was performed on liver sections. The SPSS program was used for all statistical analyses, and statistical significance was considered if a P-value < 0.05.RESULTS Significantly higher serum ferritin and lower serum hepcidin levels were detected in all groups of HBV-infected patients compared with healthy controls. Serum iron, total iron binding capacity, and serum transferrin levels were significantly lower in patients with cirrhosis and hepatocellular carcinoma, whereas the hepcidin level was higher than that in chronic hepatitis B patients. Correlation analysis indicated that serum hepcidin was negatively correlated with HBV-DNA load(P < 0.01). Serum ferritin and transferrin saturation levels increased proportionally to the extent of liver cirrhosis and poorer Child-Pugh scores(P < 0.05). The decreased serum iron and transferrin saturation levels were significantly correlated with a smaller hepatocellular carcinoma tumor burden according to Barcelona Clinic Liver Cancer staging. Liver histology showed a clearly increasing trend in iron deposition in the liver tissues with increased fibrosis, which became prominent at stages 3(severe liver fibrosis) and 4(cirrhosis). CONCLUSION Iron metabolism disorders occur in patients with HBVrelated liver diseases. The serum markers of iron metabolism disorders vary in different stages of HBV-related liver diseases.展开更多
Over the last 30 years there have been numerous worldwide investigators involved in cancer research. Billions of dollars have been spent on drug development and cancer research;however, with all of the new agents and ...Over the last 30 years there have been numerous worldwide investigators involved in cancer research. Billions of dollars have been spent on drug development and cancer research;however, with all of the new agents and modalities of treatment, we have honestly not significantly improved the overall survival of the Stage IV cancer patient. There is and will not be a magic bullet treatment, thus the extensive title of this paper. We are convinced that unless we use multiple innovative therapies in combination with conventional treatment, we will never truly defeat this disease. We have attempted to address this problem by presenting in detail some of these complex mechanisms involved in tumorigenesis, progression, escape, and metastasis. Most investigators have their own special area of interest, but if we are to conquer this scourge, we must develop an extensive, multifaceted, comprehensive approach. Hopefully this article will contribute to awareness and further insight into this very serious and complicated problem, so we can improve quality of life and improve the survival of the Stage IV cancer patient.展开更多
BACKGROUND Liver transplantation(LT)is the best treatment for patients with liver cancer or end stage cirrhosis,but it is still associated with a significant mortality.Therefore identifying factors associated with mor...BACKGROUND Liver transplantation(LT)is the best treatment for patients with liver cancer or end stage cirrhosis,but it is still associated with a significant mortality.Therefore identifying factors associated with mortality could help improve patient management.The impact of iron metabolism,which could be a relevant therapeutic target,yield discrepant results in this setting.Previous studies suggest that increased serum ferritin is associated with higher mortality.Surprisingly iron deficiency which is a well described risk factor in critically ill patients has not been considered.AIM To assess the impact of pre-transplant iron metabolism parameters on posttransplant survival.METHODS From 2001 to 2011,553 patients who underwent LT with iron metabolism parameters available at LT evaluation were included.Data were prospectively recorded at the time of evaluation and at the time of LT regarding donor and recipient.Serum ferritin(SF)and transferrin saturation(TS)were studied as continuous and categorical variable.Cox regression analysis was used to determine mortality risks factors.Follow-up data were obtained from the local and national database regarding causes of death.RESULTS At the end of a 95-mo median follow-up,196 patients were dead,38 of them because of infections.In multivariate analysis,overall mortality was significantly associated with TS>75%[HR:1.73(1.14;2.63)],SF<100μg/L[HR:1.62(1.12;2.35)],hepatocellular carcinoma[HR:1.58(1.15;2.26)],estimated glomerular filtration rate(CKD EPI Cystatin C)[HR:0.99(0.98;0.99)],and packed red blood cell transfusion[HR:1.05(1.03;1.08)].Kaplan Meier curves show that patients with low SF(<100μg/L)or high SF(>400μg/L)have lower survival rates at 36 mo than patients with normal SF(P=0.008 and P=0.016 respectively).Patients with TS higher than 75%had higher mortality at 12 mo(91.4%±1.4%vs 84.6%±3.1%,P=0.039).TS>75%was significantly associated with infection related death[HR:3.06(1.13;8.23)].CONCLUSION Our results show that iron metabolism imbalance(either deficiency or overload)is associated with post-transplant overall and infectious mortality.Impact of iron supplementation or depletion should be assessed in prospective study.展开更多
Effects of the nanocomposite and its components (magnetic fluid, cisplatin) on the level of endogenous iron exchange and the key links of genetic and epigenetic regulation of apoptotic program of sensitive and resista...Effects of the nanocomposite and its components (magnetic fluid, cisplatin) on the level of endogenous iron exchange and the key links of genetic and epigenetic regulation of apoptotic program of sensitive and resistant MCF-7 cells were examined. We showed genetic and epigenetic mechanisms of action of nanocomposite of magnetic fluid and cisplatin. Nanocomposite caused elevation of number of cells in apoptosis in sensitive and especially resistant MCF-7 cells compared to cisplatin alone. It was proved that impact of nanocomposite on MCF-7/S and MCF-7/DDP cells caused more significant changes in expression of apoptosis regulators p53, Bcl-2 and Bax. We also suggested that changes in endogenous iron homeostasis and activation of free radical processes caused significant impact on apoptosis. Those changes included changes in methylation and expression of transferrin, its receptors, ferritin heavy and light chains (predominantly in resistant cell line), which caused activation of free radical synthesis and development of oxidative stress. We also showed that nanocomposite impact resulted into significant changes in expression of miRNA-34a and miRNA-200b, which regulated apoptosis, cell adhesion, invasion and activity of ferritin heavy chains gene. Thus, use of nanocomposite containing cisplatin and ferromagnetic as exogenous source of Fe ions caused changes of endogenous iron levels in sensitive and resistant cells allowing to increase specific activity of cytostatics and overcome factors, which promoted MDR development. Pharmacocorrection of endogenous iron metabolism allowed increasing antitumor activity of cisplatin and overcoming drug resistance.展开更多
The anemia of chronic kidney disease and hemodialysis is characterized by chronic inflammation and release of cytokines,resulting in the upregulation of the iron hormone hepcidin,also increased by iron therapy and red...The anemia of chronic kidney disease and hemodialysis is characterized by chronic inflammation and release of cytokines,resulting in the upregulation of the iron hormone hepcidin,also increased by iron therapy and reduced glomerular filtration,with consequent reduction in iron absorption,recycling,and availability to the erythron.This response proves advantageous in the short-term to restrain iron availability to pathogens,but ultimately leads to severe anemia,and impairs the response to erythropoietin(Epo)and iron.Homozygosity for the common C282Y and H63D HFE polymorphisms influence iron metabolism by hampering hepcidin release by hepatocytes in response to increased iron stores,thereby resulting in inadequate inhibition of the activity of Ferroportin-1,inappropriately high iron absorption and recycling,and iron overload.However,in hemodialysis patients,carriage of HFE mutations may confer an adaptive benefit by decreasing hepcidin release in response to iron infusion and inflammation,thereby improving iron availability to erythropoiesis,anemia control,the response to Epo,and possibly survival.Therefore,anti-hepcidin therapies may improve anemia management in hemodialysis.However,HFE mutations directly favor hemoglobinization independently of hepcidin,and reduce macrophages activation in response to inflammation,whereas hepcidin might also play a beneficial anti-inflammatory and anti-microbic action during sepsis,so that direct inhibition of HFEmediated regulation of iron metabolism may represent a valuable alternative therapeutic target.Genetic studies may offer a valuable tool to test these hypotheses and guide the research of new therapies.展开更多
Objective:To investigate the correlation of hepcidin content with iron metabolism, inflammatory response and immune response in patients with rheumatoid arthritis combined with anemia.Methods: A total of 50 patients w...Objective:To investigate the correlation of hepcidin content with iron metabolism, inflammatory response and immune response in patients with rheumatoid arthritis combined with anemia.Methods: A total of 50 patients with rheumatoid arthritis combined with anemia who were treated in our hospital between September 2014 and December 2017 were selected as as the study group and 48 patients with rheumatoid arthritis alone who were treated in our hospital during the same period were selected as the control group. The differences in serum levels of hepcidin (Hepc), iron metabolism indexes, inflammatory factors and immune response indexes were compared between the two groups of patients, and Pearson test was adopted to assess the correlation between Hepc content and disease activity.Results: Serum Hepc level of study group was higher than that of control group;serum iron metabolism index SF level was lower than that of control group whereas TF and TIBC levels were higher than those of control group;serum inflammatory factors IL-1α, TNF-α and MCP-1 levels were higher than those of control group whereas IL-4 and IL-10 levels were lower than those of control group;serum immune response indexes IgG and C3 levels were higher than those of control group. The serum Hepc content of patients with RA was directly correlated with the contents of iron metabolism indexes, inflammatory factors and immune response indexes.Conclusion:Hepc level abnormally increases in patients with rheumatoid arthritis combined with anemia, and it is directly correlated with the abnormality of iron metabolism, inflammatory response and immune response.展开更多
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 divid...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 diabetic group(n=20 each). The rats were evaluated physiologically and biochemically. The hepatic histopathological changes were observed using haematoxylin and eosin(HE) staining. The m RNA expression 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 analyzed 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(s Tf R):ferritin ratio among the three groups(P>0.05). The real-time RT-PCR, immunohistochemistry and Western blotting results all revealed 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 hepcidin m RNA between non-diabetic obese group and type 2 diabetic group showed no significant difference(P>0.05). However, the protein expression levels of hepcidin in type 2 diabetic group were significantly higher than those in non-diabetic obese group(P<0.05). Compared to control group, the expression levels of IL-6 m RNA in non-diabetic obese group and type 2 diabetic group were increased significantly and the expression levels of Fpn m RNA decreased(P<0.05). However, the expression levels of HIF m RNA 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 expression of hepcidin in chronic inflammatory status. The increased hepcidin may restrain the iron release from the cells by affecting the expression of Fpn, which probably associates with the development of diabetic complication.展开更多
To verify the dynamic expressions of iron transporters during ALS progression,we investigated the expression and co-localization of divalent metal transporter 1(DMT1),ferroportin 1(FPN1)and iron regulatory protein 1(I...To verify the dynamic expressions of iron transporters during ALS progression,we investigated the expression and co-localization of divalent metal transporter 1(DMT1),ferroportin 1(FPN1)and iron regulatory protein 1(IRP1)in the spinal cord of transgenic mice harboring hSOD1G93A gene mutation(ALS mice)and non-transgenic littermates(WT mice)at 70 d,95 d and 122 d.Western blotting showed that in spinal cord of ALS mice,DMT1 was down-regulated from 70 d.FPN1 was transiently up-regulated at 70 d,and declined at 95 d and 122 d.展开更多
Objective To investigate the multiple iron metabolism-related genes expression,its regulation by iron and the expression correlation among the genes in rat tissues.Methods Two groups(n=30) of Sprague-Dawley female wea...Objective To investigate the multiple iron metabolism-related genes expression,its regulation by iron and the expression correlation among the genes in rat tissues.Methods Two groups(n=30) of Sprague-Dawley female weanling rats were fed with a control diet and an iron deficient diet respectively for 4 weeks.All rats were then sacrificed,and blood and tissue samples were collected.The routine blood examination was performed with a veterinary automatic blood cell analyzer.Elemental iron levels in liver,spleen and serum were determined by atomic absorption spectrophotometry.The mRNA expression of genes was detected by real-time fluorescence quantitative PCR.Results After 4 weeks,the hemoglobin(Hb) level and red blood cell(RBC) count were significantly lower in the iron deficient group compared with those in the control group.The iron levels in liver,spleen and serum in the iron deficient group were significantly lower than those in the control group.In reference to small intestine,the relative expression of each iron-related gene varied in the different tissues.Under the iron deficiency,the expression of these genes changed in a tissue-specific manner.The expression of most of the genes significantly correlated in intestine,spleen and lung,but few correlated in liver,heart and kidney.Conclusion Findings from our study provides new understandings about the relative expression,regulation by iron and correlation among the mRNA expressions of transferrin receptors 1 and 2,divalent metal transporter 1,ferritin,iron regulation proteins 1 and 2,hereditary hemochromatosis protein,hepcidin,ferroportin 1 and hephaestin in intestine,liver,spleen,kidney,heart,and lung of rat.展开更多
Glutamic acid and gamma-aminobutyric acid (GABA) influence iron content in the substantia nigra and globus pallidus, although the mechanisms of action remain unclear. The present study measured iron content and change...Glutamic acid and gamma-aminobutyric acid (GABA) influence iron content in the substantia nigra and globus pallidus, although the mechanisms of action remain unclear. The present study measured iron content and changes in divalent metal transporter 1 (DMT1) and hephaestin expression in the substantia nigra and caudate putamen, and explored the effects of GABA and glutamic acid on iron metabolism. Results demonstrated that iron content and DMT1 non iron response element [DMT1(-IRE)] expression were significantly greater but hephaestin expression was significantly lower in the caudate putamen of the monosodium glutamate group compared with the control group. No significant difference in iron content was detected between the GABA and control groups. DMT1(-IRE) expression was significantly reduced, but hephaestin expression was significantly increased in the GABA group compared with the control group. In addition, there was no significant difference in tyrosine hydroxylase expression between monosodium glutamate and GABA groups and the control group. These results suggested that glutamate affected iron metabolism in the caudate putamen by increasing DMT1(-IRE) and decreasing hephaestin expression. In addition, GABA decreased DMT1(-IRE) expression in the caudate putamen.展开更多
Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq dat...Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq data were obtained from ten HCC tumor samples totaling 64,545 cells and 65 glycogen metabolism genes were analyzed bya nonnegative matrix factorization(NMF).The prognosis and immune response of new glycogen TME cell dusters were predicted by using HCC and immunotherapy cohorts from public databases.HOC single cell analysis was divided into fibroblasts,NT T cells,macrophages,endothelial clls,and B cells,which were separately divided into new cell clusters by glycogen metabolism gene annotation.Pseudo temporal trajectory analysis demonstrated the temporal differentiation trajectory of different glycogen subtype cell dusters.Cellular communication analysis revealed extensive interactions between endothelial cells with glycogen metabolizing TME cell.related subtypes and diferent glycogen subtype cell clusters.SCENIC analysis of transcription factors upstream of TME cell clusters with different glycogen metabolism.In addition,TME cell dusters of glycogen metabolism were found to be enriched in expression in CAF subtypes,CD8 depleted,M1,and M2 types.Bulk seq analysis showed the prognostic signifcance of glycogen metabolism.mediated TME cell dusters in HCC,while a significant immune response was found in the immunotherapy cohort in patients treated with immune checkpoint blockade(ICB),especially for CAFs,T cells,and macrophages In summary,our study reveals for the first time that glycogen metabolism mediates intercellular communication in the hepatocellular carcinoma microenvironment while elucidating the anti-tumor mechanisms and immune prognostic responses of different subtypes of cell dusters.展开更多
The gut microbiota-brain axis has emerged as a novel target for Alzheimer's disease(AD),a neurodegenerative disease characterised by behavioural and cognitive impairment.However,most previous microbiome-based inte...The gut microbiota-brain axis has emerged as a novel target for Alzheimer's disease(AD),a neurodegenerative disease characterised by behavioural and cognitive impairment.However,most previous microbiome-based intervention studies have focused on single factors and yielded only modest cognitive improvements.Here,we proposed a multidomain intervention strategy that combined Bifidobacterium breve treatment with environmental enrichment(EE)training.In this study,we found that compared with EE or B.breve treatment alone,B.breve intervention combined with EE amplified its neuroprotective effects on AD mice,as reflected by improved cognition,inhibited neuroinflammation and enhanced synaptic function.Moreover,using microbiome and metabolome profiling,we found that the combination of B.breve and EE treatment restored AD-related gut microbiota dysbiosis and reversed microbial metabolite changes.Finally,by integrating behavioural and neurological data with metabolomic profiles,we revealed that the underlying mechanism may involve the modulation of microbiota-derived glutamine metabolism via gut-brain interactions.Collectively,combined B.breve intervention with EE treatment can alleviate AD-related cognitive impairment and improve brain function by regulating glutamine metabolism of the gut microbiome.Our findings provide a promising multidomain intervention strategy,with a combination of dietary microbiome-based and lifestyle-targeted interventions,to promote brain function and delay the progression of AD.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
In recent years,innate-like T-cell populations,such as invariant natural killer T(iNKT)cells and mucosal-associated invariant T(MAIT)cells,have been identified[1].These cells are different from conventional T cells in...In recent years,innate-like T-cell populations,such as invariant natural killer T(iNKT)cells and mucosal-associated invariant T(MAIT)cells,have been identified[1].These cells are different from conventional T cells in that they reside in tissues such as the liver,lung,and skin,rather than the lymph node and spleen[2].Although iNKT and MAIT cells are abundant in the skin immediately after birth,the detailed functions or the mechanisms regulating their localization have not been clarified[3].In a study published in Nature Immunology,Wang et al.reported that the early homing of iNKT cells to the skin was dependent on CCR10 expression during the stage of thymic development and was critical for proper commensal bacterial colonization and skin development[4].展开更多
基金supported by Academic Leader Training Program of Pudong New Area Health System in Shanghai(Grant No.PWRd2021-13).
文摘The impact of different iron metabolism processes(DIMP)on ovarian cancer remains unclear.In this study,we employed various gene chips and databases to investigate the role of DIMP in the initiation and development of ovarian cancer.cBioPortal was used to determine mutations in DIMP-associated genes in ovarian cancer.Kaplan-Meier plotter was used to examine the influence of DIMP on the prognosis of ovarian cancer.By analyzing 1669 serous ovarian cancer cases,we identified a range of mutations in iron metabolism genes,notably in those coding for the transferrin receptor(19%),melanotransferrin(19%),and ceruloplasmin(10%)in the iron import process,and glucose-6-phosphate isomerase(9%),hepcidin antimicrobial peptide(9%),metal regulatory transcription factor 1(8%),and bone morphogenetic protein 6(8%)in the iron regulation process.Compared to the unaltered group,the group with gene alterations exhibited a higher tumor mutation burden count(43 vs.54)and more advanced histologic grade(78.19%vs.87.90%).Compared to the normal ovarian counterparts,a reduction in expression was observed in 9 out of the 14 genes involved in iron utilization and 4 out of the 5 genes involved in iron export in ovarian cancer;in contrast,an increase in expression was observed in 2 out of the 3 genes involved in iron storage in ovarian cancer.Furthermore,in cisplatin-resistant cells compared to cisplatin-sensitive ones,the expression of all genes in iron storage and 13 out of 14 genes in iron import was decreased,while that of 8 out of the 10 genes in iron utilization was increased.In addition,survival curve analysis indicated that a higher expression in the majority of genes in the iron import process(12/21),or a reduced expression in most genes in the iron export process(4/5)correlated with poor progression-free survival.Additionally,TGF-βcould regulate the expression of most iron metabolism-associated genes;particularly,expression of genes involved in the iron storage process(2/2)was inhibited after TGF-β1 or TGF-β2 treatment.In conclusion,DIMP plays multifaceted roles in the initiation,chemo-resistance,and prognosis of ovarian cancer.Therapeutically targeting DIMP may pave the way for more tailored treatment approaches for ovarian cancer.
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.
文摘Introduction: Sickle cell disease is the most common genetic disease in the world, particularly in sub-Saharan Africa. It is a protean condition with multiple complications including disturbed iron metabolism. Objectives: To determine the prevalence of iron metabolism abnormalities in children with homozygous sickle cell disease, to describe the epidemiological, clinical and paraclinical characteristics of children with these abnormalities and to identify associated factors. Patients and Methods: This was a cross-sectional analytical study conducted over 9 months in the mother-child consultation unit of the Brazzaville University Hospital, the National Reference Centre for Sickle Cell Disease and the paediatric department of the Blanche Gomes mother-child hospital. It concerned children aged between 3 months and 15 years followed up for homozygous sickle cell disease. The study was based on a haemogram, iron metabolism test, LDH, transaminases and CRP. Results: The overall prevalence of iron metabolism abnomalities was 40.7%. Of the 145 children included, 35.9% had iron overload and 4.8% iron deficiency. Iron overload was associated with infections, undernutrition, iron supplementation and number of blood transfusions. Iron deficiency was not significantly associated with any factor but recurrent infections were relatively more frequent. Conclusion: Abnormalities of iron metabolism in sickle cell patients are relatively frequent, which justifies monitoring during follow-up for early detection and better management. .
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.
文摘Iron is essential for all organisms including microbial,cancer and human cells. More than a quarter of the human population is affected by abnormalities of iron metabolism, mainly from iron deficiency and iron overload. Iron also plays an important role in free radical pathology and oxidative damage which is observed in almost all major diseases, cancer and ageing. New developments include the complete treatment of iron overload and reduction of morbidity and mortality in thalassaemia using deferiprone and selected deferiprone/deferoxamine combinations and also the use of the maltol iron complex in the treatment of iron deficiency anaemia. There is also a prospect of using deferiprone as a universal antioxidant in non iron overloaded diseases such as neurodegenerative, cardiovascular, renal, infectious diseases and cancer. New regulatory molecules of iron metabolism such as endogenous and dietary chelating molecules, hepcidin, mitochondrial ferritin and their role in health and disease is under evaluation. Similarly, new mechanisms of iron deposition, removal, distribution and toxicity have been identified using new techniques such as magnetic resonance imaging increasing our understanding of iron metabolic processes and the targeted treatment of related diseases. The uniform distribution of iron in iron overload between organs and within each organ is no longer valid. Several other controversies such as the toxicity impact of non transferrin bound iron vs injected iron, the excess levels of iron in tissues causing toxicity and the role of chelation on iron absorption need further investigation. Commercial interests of pharmaceutical companies and connections to leading journals are playing a crucial role in shaping worldwide medical opinion on drug sales and use but also patients' therapeutic outcome and safety. Major controversies include the selection criteria and risk/benefit assessment in the use of deferasirox in thalassaemia and more so in idiopathic haemochromatosis, thalassaemia intermedia and ex-thalassaemia transplanted patients who are safely treated with venesection. Iron chelating drugs can override normal regulatory pathways, correct iron imbalance and minimise iron toxicity. The use of iron chelating drugs as main, alternative or adjuvant therapy is in progress in many conditions, especially those with non established or effective therapies.
基金Supported by the National Science and Technology Major Project,No.2014ZX10002002 and No.2017ZX10202202the National Key Research Plan "Precision Medicine Research" Key Project,No.2017YFC0908103+1 种基金the National Natural Science Foundation of China,No.81700534Program for JLU Science and Technology Innovative Research Team,No.2017TD-08
文摘AIM To investigate the relationship between levels of iron metabolism markers and hepatitis B virus(HBV)-related chronic liver diseases.METHODS This case-control study with 318 participants included 78 cases of chronic hepatitis B, 85 cases of HBV-related liver cirrhosis, 77 cases of HBV-related hepatocellular carcinoma, and 78 healthy controls. Markers of iron metabolism were detected in participants. Hematological and biochemical parameters and HBV-DNA were assessed. Child-Pugh grade and Barcelona Clinic Liver Cancer stage were determined for each hepatocellular carcinoma patient. Perls' staining was performed on liver sections. The SPSS program was used for all statistical analyses, and statistical significance was considered if a P-value < 0.05.RESULTS Significantly higher serum ferritin and lower serum hepcidin levels were detected in all groups of HBV-infected patients compared with healthy controls. Serum iron, total iron binding capacity, and serum transferrin levels were significantly lower in patients with cirrhosis and hepatocellular carcinoma, whereas the hepcidin level was higher than that in chronic hepatitis B patients. Correlation analysis indicated that serum hepcidin was negatively correlated with HBV-DNA load(P < 0.01). Serum ferritin and transferrin saturation levels increased proportionally to the extent of liver cirrhosis and poorer Child-Pugh scores(P < 0.05). The decreased serum iron and transferrin saturation levels were significantly correlated with a smaller hepatocellular carcinoma tumor burden according to Barcelona Clinic Liver Cancer staging. Liver histology showed a clearly increasing trend in iron deposition in the liver tissues with increased fibrosis, which became prominent at stages 3(severe liver fibrosis) and 4(cirrhosis). CONCLUSION Iron metabolism disorders occur in patients with HBVrelated liver diseases. The serum markers of iron metabolism disorders vary in different stages of HBV-related liver diseases.
文摘Over the last 30 years there have been numerous worldwide investigators involved in cancer research. Billions of dollars have been spent on drug development and cancer research;however, with all of the new agents and modalities of treatment, we have honestly not significantly improved the overall survival of the Stage IV cancer patient. There is and will not be a magic bullet treatment, thus the extensive title of this paper. We are convinced that unless we use multiple innovative therapies in combination with conventional treatment, we will never truly defeat this disease. We have attempted to address this problem by presenting in detail some of these complex mechanisms involved in tumorigenesis, progression, escape, and metastasis. Most investigators have their own special area of interest, but if we are to conquer this scourge, we must develop an extensive, multifaceted, comprehensive approach. Hopefully this article will contribute to awareness and further insight into this very serious and complicated problem, so we can improve quality of life and improve the survival of the Stage IV cancer patient.
文摘BACKGROUND Liver transplantation(LT)is the best treatment for patients with liver cancer or end stage cirrhosis,but it is still associated with a significant mortality.Therefore identifying factors associated with mortality could help improve patient management.The impact of iron metabolism,which could be a relevant therapeutic target,yield discrepant results in this setting.Previous studies suggest that increased serum ferritin is associated with higher mortality.Surprisingly iron deficiency which is a well described risk factor in critically ill patients has not been considered.AIM To assess the impact of pre-transplant iron metabolism parameters on posttransplant survival.METHODS From 2001 to 2011,553 patients who underwent LT with iron metabolism parameters available at LT evaluation were included.Data were prospectively recorded at the time of evaluation and at the time of LT regarding donor and recipient.Serum ferritin(SF)and transferrin saturation(TS)were studied as continuous and categorical variable.Cox regression analysis was used to determine mortality risks factors.Follow-up data were obtained from the local and national database regarding causes of death.RESULTS At the end of a 95-mo median follow-up,196 patients were dead,38 of them because of infections.In multivariate analysis,overall mortality was significantly associated with TS>75%[HR:1.73(1.14;2.63)],SF<100μg/L[HR:1.62(1.12;2.35)],hepatocellular carcinoma[HR:1.58(1.15;2.26)],estimated glomerular filtration rate(CKD EPI Cystatin C)[HR:0.99(0.98;0.99)],and packed red blood cell transfusion[HR:1.05(1.03;1.08)].Kaplan Meier curves show that patients with low SF(<100μg/L)or high SF(>400μg/L)have lower survival rates at 36 mo than patients with normal SF(P=0.008 and P=0.016 respectively).Patients with TS higher than 75%had higher mortality at 12 mo(91.4%±1.4%vs 84.6%±3.1%,P=0.039).TS>75%was significantly associated with infection related death[HR:3.06(1.13;8.23)].CONCLUSION Our results show that iron metabolism imbalance(either deficiency or overload)is associated with post-transplant overall and infectious mortality.Impact of iron supplementation or depletion should be assessed in prospective study.
文摘Effects of the nanocomposite and its components (magnetic fluid, cisplatin) on the level of endogenous iron exchange and the key links of genetic and epigenetic regulation of apoptotic program of sensitive and resistant MCF-7 cells were examined. We showed genetic and epigenetic mechanisms of action of nanocomposite of magnetic fluid and cisplatin. Nanocomposite caused elevation of number of cells in apoptosis in sensitive and especially resistant MCF-7 cells compared to cisplatin alone. It was proved that impact of nanocomposite on MCF-7/S and MCF-7/DDP cells caused more significant changes in expression of apoptosis regulators p53, Bcl-2 and Bax. We also suggested that changes in endogenous iron homeostasis and activation of free radical processes caused significant impact on apoptosis. Those changes included changes in methylation and expression of transferrin, its receptors, ferritin heavy and light chains (predominantly in resistant cell line), which caused activation of free radical synthesis and development of oxidative stress. We also showed that nanocomposite impact resulted into significant changes in expression of miRNA-34a and miRNA-200b, which regulated apoptosis, cell adhesion, invasion and activity of ferritin heavy chains gene. Thus, use of nanocomposite containing cisplatin and ferromagnetic as exogenous source of Fe ions caused changes of endogenous iron levels in sensitive and resistant cells allowing to increase specific activity of cytostatics and overcome factors, which promoted MDR development. Pharmacocorrection of endogenous iron metabolism allowed increasing antitumor activity of cisplatin and overcoming drug resistance.
文摘The anemia of chronic kidney disease and hemodialysis is characterized by chronic inflammation and release of cytokines,resulting in the upregulation of the iron hormone hepcidin,also increased by iron therapy and reduced glomerular filtration,with consequent reduction in iron absorption,recycling,and availability to the erythron.This response proves advantageous in the short-term to restrain iron availability to pathogens,but ultimately leads to severe anemia,and impairs the response to erythropoietin(Epo)and iron.Homozygosity for the common C282Y and H63D HFE polymorphisms influence iron metabolism by hampering hepcidin release by hepatocytes in response to increased iron stores,thereby resulting in inadequate inhibition of the activity of Ferroportin-1,inappropriately high iron absorption and recycling,and iron overload.However,in hemodialysis patients,carriage of HFE mutations may confer an adaptive benefit by decreasing hepcidin release in response to iron infusion and inflammation,thereby improving iron availability to erythropoiesis,anemia control,the response to Epo,and possibly survival.Therefore,anti-hepcidin therapies may improve anemia management in hemodialysis.However,HFE mutations directly favor hemoglobinization independently of hepcidin,and reduce macrophages activation in response to inflammation,whereas hepcidin might also play a beneficial anti-inflammatory and anti-microbic action during sepsis,so that direct inhibition of HFEmediated regulation of iron metabolism may represent a valuable alternative therapeutic target.Genetic studies may offer a valuable tool to test these hypotheses and guide the research of new therapies.
文摘Objective:To investigate the correlation of hepcidin content with iron metabolism, inflammatory response and immune response in patients with rheumatoid arthritis combined with anemia.Methods: A total of 50 patients with rheumatoid arthritis combined with anemia who were treated in our hospital between September 2014 and December 2017 were selected as as the study group and 48 patients with rheumatoid arthritis alone who were treated in our hospital during the same period were selected as the control group. The differences in serum levels of hepcidin (Hepc), iron metabolism indexes, inflammatory factors and immune response indexes were compared between the two groups of patients, and Pearson test was adopted to assess the correlation between Hepc content and disease activity.Results: Serum Hepc level of study group was higher than that of control group;serum iron metabolism index SF level was lower than that of control group whereas TF and TIBC levels were higher than those of control group;serum inflammatory factors IL-1α, TNF-α and MCP-1 levels were higher than those of control group whereas IL-4 and IL-10 levels were lower than those of control group;serum immune response indexes IgG and C3 levels were higher than those of control group. The serum Hepc content of patients with RA was directly correlated with the contents of iron metabolism indexes, inflammatory factors and immune response indexes.Conclusion:Hepc level abnormally increases in patients with rheumatoid arthritis combined with anemia, and it is directly correlated with the abnormality of iron metabolism, inflammatory response and immune response.
文摘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 diabetic group(n=20 each). The rats were evaluated physiologically and biochemically. The hepatic histopathological changes were observed using haematoxylin and eosin(HE) staining. The m RNA expression 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 analyzed 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(s Tf R):ferritin ratio among the three groups(P>0.05). The real-time RT-PCR, immunohistochemistry and Western blotting results all revealed 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 hepcidin m RNA between non-diabetic obese group and type 2 diabetic group showed no significant difference(P>0.05). However, the protein expression levels of hepcidin in type 2 diabetic group were significantly higher than those in non-diabetic obese group(P<0.05). Compared to control group, the expression levels of IL-6 m RNA in non-diabetic obese group and type 2 diabetic group were increased significantly and the expression levels of Fpn m RNA decreased(P<0.05). However, the expression levels of HIF m RNA 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 expression of hepcidin in chronic inflammatory status. The increased hepcidin may restrain the iron release from the cells by affecting the expression of Fpn, which probably associates with the development of diabetic complication.
文摘To verify the dynamic expressions of iron transporters during ALS progression,we investigated the expression and co-localization of divalent metal transporter 1(DMT1),ferroportin 1(FPN1)and iron regulatory protein 1(IRP1)in the spinal cord of transgenic mice harboring hSOD1G93A gene mutation(ALS mice)and non-transgenic littermates(WT mice)at 70 d,95 d and 122 d.Western blotting showed that in spinal cord of ALS mice,DMT1 was down-regulated from 70 d.FPN1 was transiently up-regulated at 70 d,and declined at 95 d and 122 d.
基金supported by the National Natural Science Foundation of China (No.30800909)the Fundamental Research Funds for the Central Universities
文摘Objective To investigate the multiple iron metabolism-related genes expression,its regulation by iron and the expression correlation among the genes in rat tissues.Methods Two groups(n=30) of Sprague-Dawley female weanling rats were fed with a control diet and an iron deficient diet respectively for 4 weeks.All rats were then sacrificed,and blood and tissue samples were collected.The routine blood examination was performed with a veterinary automatic blood cell analyzer.Elemental iron levels in liver,spleen and serum were determined by atomic absorption spectrophotometry.The mRNA expression of genes was detected by real-time fluorescence quantitative PCR.Results After 4 weeks,the hemoglobin(Hb) level and red blood cell(RBC) count were significantly lower in the iron deficient group compared with those in the control group.The iron levels in liver,spleen and serum in the iron deficient group were significantly lower than those in the control group.In reference to small intestine,the relative expression of each iron-related gene varied in the different tissues.Under the iron deficiency,the expression of these genes changed in a tissue-specific manner.The expression of most of the genes significantly correlated in intestine,spleen and lung,but few correlated in liver,heart and kidney.Conclusion Findings from our study provides new understandings about the relative expression,regulation by iron and correlation among the mRNA expressions of transferrin receptors 1 and 2,divalent metal transporter 1,ferritin,iron regulation proteins 1 and 2,hereditary hemochromatosis protein,hepcidin,ferroportin 1 and hephaestin in intestine,liver,spleen,kidney,heart,and lung of rat.
基金the National Natural Science Foundation of China, No. 30570957the Natural Science Foundation of Hebei Province, No. C2006000152, C2007000251
文摘Glutamic acid and gamma-aminobutyric acid (GABA) influence iron content in the substantia nigra and globus pallidus, although the mechanisms of action remain unclear. The present study measured iron content and changes in divalent metal transporter 1 (DMT1) and hephaestin expression in the substantia nigra and caudate putamen, and explored the effects of GABA and glutamic acid on iron metabolism. Results demonstrated that iron content and DMT1 non iron response element [DMT1(-IRE)] expression were significantly greater but hephaestin expression was significantly lower in the caudate putamen of the monosodium glutamate group compared with the control group. No significant difference in iron content was detected between the GABA and control groups. DMT1(-IRE) expression was significantly reduced, but hephaestin expression was significantly increased in the GABA group compared with the control group. In addition, there was no significant difference in tyrosine hydroxylase expression between monosodium glutamate and GABA groups and the control group. These results suggested that glutamate affected iron metabolism in the caudate putamen by increasing DMT1(-IRE) and decreasing hephaestin expression. In addition, GABA decreased DMT1(-IRE) expression in the caudate putamen.
基金Liuzhou City's Top Ten Hundred Talents Project,Liuzhou Science and Technology Project(Grant Nos.2021CBC0126 and 2021CBC0123)Guangxi Zhuang Autonomous Region Health and Family Planning Commission Projects(Z20210561,Z20210903)+1 种基金liuzhou Scienceand Technology Plan Projects(2021CBC0121,2021CBC0128).
文摘Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq data were obtained from ten HCC tumor samples totaling 64,545 cells and 65 glycogen metabolism genes were analyzed bya nonnegative matrix factorization(NMF).The prognosis and immune response of new glycogen TME cell dusters were predicted by using HCC and immunotherapy cohorts from public databases.HOC single cell analysis was divided into fibroblasts,NT T cells,macrophages,endothelial clls,and B cells,which were separately divided into new cell clusters by glycogen metabolism gene annotation.Pseudo temporal trajectory analysis demonstrated the temporal differentiation trajectory of different glycogen subtype cell dusters.Cellular communication analysis revealed extensive interactions between endothelial cells with glycogen metabolizing TME cell.related subtypes and diferent glycogen subtype cell clusters.SCENIC analysis of transcription factors upstream of TME cell clusters with different glycogen metabolism.In addition,TME cell dusters of glycogen metabolism were found to be enriched in expression in CAF subtypes,CD8 depleted,M1,and M2 types.Bulk seq analysis showed the prognostic signifcance of glycogen metabolism.mediated TME cell dusters in HCC,while a significant immune response was found in the immunotherapy cohort in patients treated with immune checkpoint blockade(ICB),especially for CAFs,T cells,and macrophages In summary,our study reveals for the first time that glycogen metabolism mediates intercellular communication in the hepatocellular carcinoma microenvironment while elucidating the anti-tumor mechanisms and immune prognostic responses of different subtypes of cell dusters.
基金supported by the National Natural Science Foundation of China(31972052,32021005,31820103010)the Fundamental Research Funds for the Central Universities(JUSRP22006,JUSRP51501)the Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province。
文摘The gut microbiota-brain axis has emerged as a novel target for Alzheimer's disease(AD),a neurodegenerative disease characterised by behavioural and cognitive impairment.However,most previous microbiome-based intervention studies have focused on single factors and yielded only modest cognitive improvements.Here,we proposed a multidomain intervention strategy that combined Bifidobacterium breve treatment with environmental enrichment(EE)training.In this study,we found that compared with EE or B.breve treatment alone,B.breve intervention combined with EE amplified its neuroprotective effects on AD mice,as reflected by improved cognition,inhibited neuroinflammation and enhanced synaptic function.Moreover,using microbiome and metabolome profiling,we found that the combination of B.breve and EE treatment restored AD-related gut microbiota dysbiosis and reversed microbial metabolite changes.Finally,by integrating behavioural and neurological data with metabolomic profiles,we revealed that the underlying mechanism may involve the modulation of microbiota-derived glutamine metabolism via gut-brain interactions.Collectively,combined B.breve intervention with EE treatment can alleviate AD-related cognitive impairment and improve brain function by regulating glutamine metabolism of the gut microbiome.Our findings provide a promising multidomain intervention strategy,with a combination of dietary microbiome-based and lifestyle-targeted interventions,to promote brain function and delay the progression of AD.
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 in part by AMED(grant numbers JP20fk0108129,JP21fk0108129h0702,and JP21lm0203007),a GSK Research grant(grant number A-32),the Japan Intractable Diseases(Nanbyo)Research Foundation(grant number 2020B02),JSPS KAKENHI(grant numbers JP21K16118 and JP21K08194),the Smoking Research Foundation(2021Y007)the Takeda Science Foundation+3 种基金the Uehara Memorial Foundation,the MSD Life Science Foundationthe Japanese Respiratory Society Boehringer Ingelheim Research Grant Programthe Foundation of Kinoshita Memorial Enterprisethe Senri Life Science Foundation,and the Inamori Foundation.
文摘In recent years,innate-like T-cell populations,such as invariant natural killer T(iNKT)cells and mucosal-associated invariant T(MAIT)cells,have been identified[1].These cells are different from conventional T cells in that they reside in tissues such as the liver,lung,and skin,rather than the lymph node and spleen[2].Although iNKT and MAIT cells are abundant in the skin immediately after birth,the detailed functions or the mechanisms regulating their localization have not been clarified[3].In a study published in Nature Immunology,Wang et al.reported that the early homing of iNKT cells to the skin was dependent on CCR10 expression during the stage of thymic development and was critical for proper commensal bacterial colonization and skin development[4].
