Iron deficiency anemia(IDA)is a major global health problem.Tegillarca granosa has been considered as an excellent source of iron given its high content of iron-binding protein,ferritin.The aim of the present study wa...Iron deficiency anemia(IDA)is a major global health problem.Tegillarca granosa has been considered as an excellent source of iron given its high content of iron-binding protein,ferritin.The aim of the present study was to determine the physicochemical properties,protein structures,and iron uptake of ferritin extracted from T.granosa,and to evaluate the potential impacts of chitosan glycosylation on these characteristics.Based on Box-Behnken design and response surface methodology,the optimal conditions for glycosylation included a ferritin/chitosan mass ratio of 4:1,a pH of 5.5,a reaction time of 10 min,and a reaction temperature of 50℃.Glycosylation caused decreased surface hydrophobicity and elevated water-holding capacity of ferritin due to the introduction of hydrophilic groups.Additionally,glycosylation improved antioxidant capacity of ferritin by 20.69%–189.66%,likely owing to the protons donated by saccharide moiety to terminate free radical chain reaction.The in vitro digestibility of ferritin was elevated by 22.56%–104.85%after glycosylation,which could be associated with lessβ-sheet content in secondary structure that made the glycosylated protein less resistant to enzymatic digestion.The results of the iron bioavailability in Caco-2 cells revealed that ferritin(78.85–231.77 ngmg^(−1))exhibited better iron bioavailability than FeSO4(51.48–114.37 ngmg^(−1))and the values were further elevated by glycosylation with chitosan(296.23–358.20 ngmg^(−1)),which may be related to the physicochemical properties of ferritin via glycosylation modification.These results provide a basis for the development of T.granosa derived ferritin and its glycosylated products,and can promote the utilization of aquatic resources.展开更多
BACKGROUND The effect of serum iron or ferritin parameters on mortality among critically ill patients is not well characterized.AIM To determine the association between serum iron or ferritin parameters and mortality ...BACKGROUND The effect of serum iron or ferritin parameters on mortality among critically ill patients is not well characterized.AIM To determine the association between serum iron or ferritin parameters and mortality among critically ill patients.METHODS Web of Science,Embase,PubMed,and Cochrane Library databases were searched for studies on serum iron or ferritin parameters and mortality among critically ill patients.Two reviewers independently assessed,selected,and abstracted data from studies reporting on serum iron or ferritin parameters and mortality among critically ill patients.Data on serum iron or ferritin levels,mortality,and demographics were extracted.RESULTS Nineteen studies comprising 125490 patients were eligible for inclusion.We observed a slight negative effect of serum ferritin on mortality in the United States population[relative risk(RR)1.002;95%CI:1.002-1.004].In patients with sepsis,serum iron had a significant negative effect on mortality(RR=1.567;95%CI:1.208-1.925).CONCLUSION This systematic review presents evidence of a negative correlation between serum iron levels and mortality among patients with sepsis.Furthermore,it reveals a minor yet adverse impact of serum ferritin on mortality among the United States population.展开更多
Objective:To investigate the difference in serum ferritin levels between deceased and surviving regular hemodialysis patients with COVID-19.Methods:We conducted a systematic search across four databases following the ...Objective:To investigate the difference in serum ferritin levels between deceased and surviving regular hemodialysis patients with COVID-19.Methods:We conducted a systematic search across four databases following the PRISMA statement guidelines.Studies reporting ferritin levels and mortality of regular hemodialysis patients with COVID-19 were included.Employing the random-effects model,we performed a meta-analysis to determine the mean difference in serum ferritin levels between the studied groups,along with their corresponding 95%confidence intervals.The meta-analysis was carried out using Review Manager 5.4 and Stata 16.Results:A total of 1013 patients from seven studies were included in this study.Our meta-analysis showed higher mean serum ferritin in the deceased compared to surviving regular hemodialysis patients with COVID-19,with a mean difference of 449.43 ng/mL[95%CI(244.07,654.80),P<0.0001;I2=58%,P=0.003].Conclusions:Our study found a higher mean of serum ferritin levels in the deceased compared to surviving regular hemodialysis patients with COVID-19.展开更多
BACKGROUND The incidence of early-onset colorectal cancer(EO-CRC)is rising in the United States,and is often diagnosed at advanced stages.Low serum ferritin is often incidentally discovered in young adults,however,the...BACKGROUND The incidence of early-onset colorectal cancer(EO-CRC)is rising in the United States,and is often diagnosed at advanced stages.Low serum ferritin is often incidentally discovered in young adults,however,the indication for endoscopy in EO-CRC is unclear.AIM To compare serum ferritin between patients with EO-CRC and healthy controls(HCs),and examine the association of serum ferritin in EO-CRC with patient-and disease-specific characteristics.METHODS A retrospective study of patients<50 years with newly-diagnosed EO-CRC was conducted from 1/2013-12/2023.Patients were included if serum ferritin was measured within 2 years prior to 1 year following CRC histologic diagnosis.To supplement the analysis,a cohort of HCs meeting similar inclusion and exclusion criteria were identified for comparison.A sensitivity analysis including only patients with serum ferritin obtained at or before diagnosis was separately performed to minimize risk of confounding.RESULTS Among 85 patients identified with EO-CRC(48 females),the median serum ferritin level was 26 ng/mL(range<1-2759 ng/mL).Compared to HCs(n=80211),there were a higher proportion of individuals with EO-CRC with serum ferritin<20 ng/mL(female 65%,male 40%)versus HCs(female 32.1%,male 7.2%)age 29-39 years(P=0.002 and P<0.00001,respectively).Stage IV disease was associated with significantly higher serum ferritin compared to less advanced stages(P<0.001).Serum ferritin obtained before or at the time of diagnosis was lower than levels obtained after diagnosis.Similar findings were confirmed in the sensitivity analysis.CONCLUSION Severe iron deficiency may indicate an increased risk of EO-CRC,particularly at earlier stages.Further studies defining the optimal serum ferritin threshold and routine incorporation of serum ferritin in screening algorithms is essential to develop more effective screening strategies for EO-CRC.展开更多
Objective Ferritin,initially acting as an iron-storage protein,was found to be associated with metabolic diseases.Our study was designed to investigate the association between serum ferritin and metabolic-associated f...Objective Ferritin,initially acting as an iron-storage protein,was found to be associated with metabolic diseases.Our study was designed to investigate the association between serum ferritin and metabolic-associated fatty liver disease(MAFLD)using data from the National Health and Nutrition Examination Survey(NHANES)of the United State of America.Methods A cross-sectional study was conducted,enrolling a total of 2145 participants from the NHANES in the 2017–2018 cycles.Hepatic steatosis and liver fibrosis were assessed by ultrasound images and several non-invasive indexes.Multiple regression analysis was conducted to determine the associations between serum ferritin concentration and MAFLD and liver fibrosis.Results The analysis revealed that participants with higher serum ferritin levels(Q3 and Q4 groups)had a higher prevalence of MAFLD than those with the lowest serum ferritin levels[Q3 vs.Q1:OR=2.17(1.33,3.53),P<0.05 in fatty liver index(FLI);Q4 vs.Q1:OR=3.13(1.91,5.13),P<0.05 in FLI].Additionally,participants with the highest serum ferritin levels(Q4 group)displayed a higher prevalence of liver fibrosis[Q4 vs.Q1:OR=2.59(1.19,5.62),P<0.05 in liver stiffness measurement;OR=5.06(1.12,22.94),P<0.05 in fibrosis-4 index],with significantly increased risk observed in participants with concomitant diabetes[OR=7.45(1.55,35.72),P=0.012].Conclusion Our study revealed that elevated serum ferritin levels are associated with a higher prevalence of MAFLD and advanced liver fibrosis in patients.Elevated serum ferritin levels combined with diabetes are important risk factors for liver fibrosis.展开更多
BACKGROUND Recently,type 2 diabetic osteoporosis(T2DOP)has become a research hotspot for the complications of diabetes,but the specific mechanism of its occurrence and development remains unknown.Ferroptosis caused by...BACKGROUND Recently,type 2 diabetic osteoporosis(T2DOP)has become a research hotspot for the complications of diabetes,but the specific mechanism of its occurrence and development remains unknown.Ferroptosis caused by iron overload is con-sidered an important cause of T2DOP.Polycytosine RNA-binding protein 1(PCBP1),an iron ion chaperone,is considered a protector of ferroptosis.AIM To investigate the existence of ferroptosis and specific role of PCBP1 in the development of type 2 diabetes.METHODS A cell counting kit-8 assay was used to detect changes in osteoblast viability under high glucose(HG)and/or ferroptosis inhibitors at different concentrations and times.Transmission electron microscopy was used to examine the morpho-logical changes in the mitochondria of osteoblasts under HG,and western blotting was used to detect the expression levels of PCBP1,ferritin,and the ferroptosis-related protein glutathione peroxidase 4(GPX4).A lentivirus silenced and overex-pressed PCBP1.Western blotting was used to detect the expression levels of the osteoblast functional proteins osteoprotegerin(OPG)and osteocalcin(OCN),whereas flow cytometry was used to detect changes in reactive oxygen species(ROS)levels in each group.RESULTS Under HG,the viability of osteoblasts was considerably decreased,the number of mitochondria undergoing atrophy was considerably increased,PCBP1 and ferritin expression levels were increased,and GPX4 expression was decreased.Western blotting results demonstrated that infection with lentivirus overexpressing PCBP1,increased the expression levels of ferritin,GPX4,OPG,and OCN,compared with the HG group.Flow cytometry results showed a reduction in ROS,and an opposite result was obtained after silencing PCBP1.CONCLUSION PCBP1 may protect osteoblasts and reduce the harm caused by ferroptosis by promoting ferritin expression under a HG environment.Moreover,PCBP1 may be a potential therapeutic target for T2DOP.展开更多
BACKGROUND Gastric cancer is a kind of malignant tumor which is prevalent all over the world.Although some progress has been made in the treatment of gastric cancer,its prognosis is still not optimistic,so it is of gr...BACKGROUND Gastric cancer is a kind of malignant tumor which is prevalent all over the world.Although some progress has been made in the treatment of gastric cancer,its prognosis is still not optimistic,so it is of great significance to find reliable prog-nostic indicators to guide the treatment and management of patients with gastric cancer.AIM To explore the relationship between serum levels of five biomarkers[carcinoem-bryonic antigen(CEA),carbohydrate antigen(CA)19-9,CA72-4,CA24-2,and ferritin]and prognosis in patients with gastric cancer.METHODS This study included 200 patients with gastric adenocarcinoma,and conducted an in-depth analysis of their baseline characteristics,relationship between tumor markers and staging,and prognosis.The study found that CA19-9 has a signi-ficant correlation with tumor stage,the average levels of CA24-2,CEA,CA72-4 and ferritin were slightly increased disregarding the stage of tumor.Survival analysis showed that increases in CEA,CA19-9,CA24-2,and ferritin were all associated with shortened overall survival of patients.Further multivariate ana-lysis revealed that elevated serum CA72-4 levels were an inde-pendent adverse prognostic factor.RESULTS This study reveals that there is a significant correlation between the expression levels of serum tumor markers CEA,CA19-9,CA72-4,CA24-2 and ferritin in patients with gastric cancer and prognosis,and can be used as important indicators for prognostic evaluation of gastric cancer.In particular,markers that appear abnormally elevated initially may help identify gastric cancer patients with poor prognosis.CONCLUSION Serum CEA and CA19-9 play an important role in the prognosis assessment of gastric cancer,and are effective tools to guide clinical practice and optimize individualized treatment strategies for gastric cancer patients.展开更多
目的利用昆虫细胞/杆状病毒系统表达细粒棘球蚴Eg95-Eg.ferritin融合蛋白,用于开发包虫病新型疫苗以及建立相关血清学诊断方法等研究。方法从细粒棘球蚴包囊中分离原头节,超声粉碎后提取总RNA为模板,通过RT-PCR扩增细粒棘球蚴Eg95和Eg.f...目的利用昆虫细胞/杆状病毒系统表达细粒棘球蚴Eg95-Eg.ferritin融合蛋白,用于开发包虫病新型疫苗以及建立相关血清学诊断方法等研究。方法从细粒棘球蚴包囊中分离原头节,超声粉碎后提取总RNA为模板,通过RT-PCR扩增细粒棘球蚴Eg95和Eg.ferritin基因,采用基因拼接法将Eg95和Eg.ferritin融合,将该融合基因Eg95-Eg.ferritin插入到p Fast Bac DUAL载体中,构建重组转座载体后转化DH10Bac感受态细胞,获得重组Bacmid质粒后转染Sf-9昆虫细胞,传毒3代,对表达蛋白进行Western blot鉴定。结果成功克隆了Eg95和Eg.ferritin基因,通过柔性氨基酸linker成功获得了融合基因Eg95-Eg.ferritin,经PCR和酶切鉴定成功构建了重组质粒p Fast Bac DUAL-Eg95-Eg.ferritin,Western blot结果证实表达蛋白能够被包虫病人标准阳性血清识别。结论在Bac-to-Bac杆状病毒表达系统中成功表达了细粒棘球蚴Eg95-Eg.ferritin融合蛋白,与包虫病人标准阳性血清具有良好的反应性。展开更多
In the present study, we used immunohistochemistry and western blot analysis to examine changes in the levels and cellular localization of iron, heavy chain ferritin（ferritin-H）, and transferrin in the gerbil hippoc...In the present study, we used immunohistochemistry and western blot analysis to examine changes in the levels and cellular localization of iron, heavy chain ferritin（ferritin-H）, and transferrin in the gerbil hippocampal CA1 region from 30 minutes to 7 days following transient forebrain ischemia. Relative to sham controls, iron reactivity increased significantly in the stratum pyramidale and stratum oriens at 12 hours following ischemic insult, transiently decreased at 1–2 days and then increased once again within the CA1 region at 4–7 days after ischemia. One day after ischemia, ferritin-H immunoreactivity increased significantly in the stratum pyramidale and decreased at 2 days. At 4–7 days after ischemia, ferritin-H immunoreactivity in the glial components in the CA1 region was significantly increased. Transferrin immunoreactivity was increased significantly in the stratum pyramidale at 12 hours, peaked at 1 day, and then decreased significantly at 2 days after ischemia. Seven days after ischemia, Transferrin immunoreactivity in the glial cells of the stratum oriens and radiatum was significantly increased. Western blot analyses supported these results, demonstrating that compared to sham controls, ferritin H and transferrin protein levels in hippocampal homogenates significantly increased at 1 day after ischemia, peaked at 4 days and then decreased. These results suggest that iron overload-induced oxidative stress is most prominent at 12 hours after ischemia in the stratum pyramidale, suggesting that this time window may be the optimal period for therapeutic intervention to protect neurons from ischemia-induced death.展开更多
Iron is an essential trophic element that is required for cell viability and differentiation, especially in oligodendrocytes, which consume relatively high rates of energy to produce myelin. Multiple iron metabolism p...Iron is an essential trophic element that is required for cell viability and differentiation, especially in oligodendrocytes, which consume relatively high rates of energy to produce myelin. Multiple iron metabolism proteins are expressed in the brain including transferrin receptor and ferritin-H. However, it is still unknown whether they are developmentally regulated in oligodendrocyte lineage cells for myelination. Here, using an in vitro cultured differentiation model of oligodendrocytes, we found that both transferrin receptor and ferritin-H are significantly upregulated during oligodendrocyte maturation, implying the essential role of iron in the development of oligodendrocytes. Additional different doses of Fe3＋ in the cultured medium did not affect oligodendrocyte precursor cell maturation or ferritin-H expression but decreased the expression of the transferrin receptor. These results indicate that upregulation of both transferrin receptor and ferritin-H contributes to maturation and myelination of oligodendrocyte precursor cells.展开更多
Background: Iron overload in association with persistent anemia is responsible for endocrine dysfunction in β-thalassemia patients, blood transfusion combined with iron-chelation can modify life quality in these chil...Background: Iron overload in association with persistent anemia is responsible for endocrine dysfunction in β-thalassemia patients, blood transfusion combined with iron-chelation can modify life quality in these children, but they tend to suffer from delayed maturity and endocrine dysfunction. Aim: This study aims to correlate degree of hypogonadism to ferritin load in regular transfused β-thalassemia patients. Methods: It was carried out on 30 β-thalassemia major (TM) patients aged 12 to 18 years, puberty was assessed clinically, blood picture on Cell-Dyne 2700, ferritin level and pattern of FSH, LH, testosterone and estradiol before and after gonadotropin (GnRH) analogue stimulation test, they were determined on ARCHITECT ABBOTT system. Results: Twenty patients had not yet achieved puberty, FSH level was 1.45 ± 1.88 mIU/ml before (GnRH) analogue and 3.78 ± 4.19 mIU/ml after 4 hours of injection. LH level was 1.91 ± 4.79 mIU/ml before (GnRH) test, while after 4 hours it was 6.52 ± 7.50 mIU/ml, 88.24% of males had low serum testosterone level, 84.6% of girls had low serum estradiol level, FSH, LH, estradiol, testosterone before and after GNRH analogue were statistically insignificant, mean ferritin level was 3344.32 ± 1142.142 ng/ml, with insignificant correlation to hormonal pattern before and after GnRH therapy. Conclusion: Iron overload and hypogonadism are the presenting data in this study, insignificant correlation between ferritin level and hormonal reserve pattern, there may be another etiology in pathophysiology of low gonadal reserve such as severe anemia, chronic disease and may be genetic predisposition underlying susceptibility to iron toxicity, which need further investigations.展开更多
The neuronal differentiation of mesenchymal stem cells offers a new strategy for the treatment of neurological disorders.Thus,there is a need to identify a noninvasive and sensitive in vivo imaging approach for real-t...The neuronal differentiation of mesenchymal stem cells offers a new strategy for the treatment of neurological disorders.Thus,there is a need to identify a noninvasive and sensitive in vivo imaging approach for real-time monitoring of transplanted stem cells.Our previous study confirmed that magnetic resonance imaging,with a focus on the ferritin heavy chain 1 reporter gene,could track the proliferation and differentiation of bone marrow mesenchymal stem cells that had been transduced with lentivirus carrying the ferritin heavy chain 1 reporter gene.However,we could not determine whether or when bone marrow mesenchymal stem cells had undergone neuronal differentiation based on changes in the magnetic resonance imaging signal.To solve this problem,we identified a neuron-specific enolase that can be differentially expressed before and after neuronal differentiation in stem cells.In this study,we successfully constructed a lentivirus carrying the neuron-specific enolase promoter and expressing the ferritin heavy chain 1 reporter gene;we used this lentivirus to transduce bone marrow mesenchymal stem cells.Cellular and animal studies showed that the neuron-specific enolase promoter effectively drove the expression of ferritin heavy chain 1 after neuronal differentiation of bone marrow mesenchymal stem cells;this led to intracellular accumulation of iron and corresponding changes in the magnetic resonance imaging signal.In summary,we established an innovative magnetic resonance imaging approach focused on the induction of reporter gene expression by a neuron-specific promoter.This imaging method can be used to noninvasively and sensitively detect neuronal differentiation in stem cells,which may be useful in stem cell-based therapies.展开更多
基金supported by the National Key R&D Program of China(No.2018YFD0901105).
文摘Iron deficiency anemia(IDA)is a major global health problem.Tegillarca granosa has been considered as an excellent source of iron given its high content of iron-binding protein,ferritin.The aim of the present study was to determine the physicochemical properties,protein structures,and iron uptake of ferritin extracted from T.granosa,and to evaluate the potential impacts of chitosan glycosylation on these characteristics.Based on Box-Behnken design and response surface methodology,the optimal conditions for glycosylation included a ferritin/chitosan mass ratio of 4:1,a pH of 5.5,a reaction time of 10 min,and a reaction temperature of 50℃.Glycosylation caused decreased surface hydrophobicity and elevated water-holding capacity of ferritin due to the introduction of hydrophilic groups.Additionally,glycosylation improved antioxidant capacity of ferritin by 20.69%–189.66%,likely owing to the protons donated by saccharide moiety to terminate free radical chain reaction.The in vitro digestibility of ferritin was elevated by 22.56%–104.85%after glycosylation,which could be associated with lessβ-sheet content in secondary structure that made the glycosylated protein less resistant to enzymatic digestion.The results of the iron bioavailability in Caco-2 cells revealed that ferritin(78.85–231.77 ngmg^(−1))exhibited better iron bioavailability than FeSO4(51.48–114.37 ngmg^(−1))and the values were further elevated by glycosylation with chitosan(296.23–358.20 ngmg^(−1)),which may be related to the physicochemical properties of ferritin via glycosylation modification.These results provide a basis for the development of T.granosa derived ferritin and its glycosylated products,and can promote the utilization of aquatic resources.
基金Supported by The National Natural Science Foundation of China,No.82104989.
文摘BACKGROUND The effect of serum iron or ferritin parameters on mortality among critically ill patients is not well characterized.AIM To determine the association between serum iron or ferritin parameters and mortality among critically ill patients.METHODS Web of Science,Embase,PubMed,and Cochrane Library databases were searched for studies on serum iron or ferritin parameters and mortality among critically ill patients.Two reviewers independently assessed,selected,and abstracted data from studies reporting on serum iron or ferritin parameters and mortality among critically ill patients.Data on serum iron or ferritin levels,mortality,and demographics were extracted.RESULTS Nineteen studies comprising 125490 patients were eligible for inclusion.We observed a slight negative effect of serum ferritin on mortality in the United States population[relative risk(RR)1.002;95%CI:1.002-1.004].In patients with sepsis,serum iron had a significant negative effect on mortality(RR=1.567;95%CI:1.208-1.925).CONCLUSION This systematic review presents evidence of a negative correlation between serum iron levels and mortality among patients with sepsis.Furthermore,it reveals a minor yet adverse impact of serum ferritin on mortality among the United States population.
文摘Objective:To investigate the difference in serum ferritin levels between deceased and surviving regular hemodialysis patients with COVID-19.Methods:We conducted a systematic search across four databases following the PRISMA statement guidelines.Studies reporting ferritin levels and mortality of regular hemodialysis patients with COVID-19 were included.Employing the random-effects model,we performed a meta-analysis to determine the mean difference in serum ferritin levels between the studied groups,along with their corresponding 95%confidence intervals.The meta-analysis was carried out using Review Manager 5.4 and Stata 16.Results:A total of 1013 patients from seven studies were included in this study.Our meta-analysis showed higher mean serum ferritin in the deceased compared to surviving regular hemodialysis patients with COVID-19,with a mean difference of 449.43 ng/mL[95%CI(244.07,654.80),P<0.0001;I2=58%,P=0.003].Conclusions:Our study found a higher mean of serum ferritin levels in the deceased compared to surviving regular hemodialysis patients with COVID-19.
基金Supported by the Oregon Health&Sciences(OHSU)Institutional Review Board,No.STUDY00026428.
文摘BACKGROUND The incidence of early-onset colorectal cancer(EO-CRC)is rising in the United States,and is often diagnosed at advanced stages.Low serum ferritin is often incidentally discovered in young adults,however,the indication for endoscopy in EO-CRC is unclear.AIM To compare serum ferritin between patients with EO-CRC and healthy controls(HCs),and examine the association of serum ferritin in EO-CRC with patient-and disease-specific characteristics.METHODS A retrospective study of patients<50 years with newly-diagnosed EO-CRC was conducted from 1/2013-12/2023.Patients were included if serum ferritin was measured within 2 years prior to 1 year following CRC histologic diagnosis.To supplement the analysis,a cohort of HCs meeting similar inclusion and exclusion criteria were identified for comparison.A sensitivity analysis including only patients with serum ferritin obtained at or before diagnosis was separately performed to minimize risk of confounding.RESULTS Among 85 patients identified with EO-CRC(48 females),the median serum ferritin level was 26 ng/mL(range<1-2759 ng/mL).Compared to HCs(n=80211),there were a higher proportion of individuals with EO-CRC with serum ferritin<20 ng/mL(female 65%,male 40%)versus HCs(female 32.1%,male 7.2%)age 29-39 years(P=0.002 and P<0.00001,respectively).Stage IV disease was associated with significantly higher serum ferritin compared to less advanced stages(P<0.001).Serum ferritin obtained before or at the time of diagnosis was lower than levels obtained after diagnosis.Similar findings were confirmed in the sensitivity analysis.CONCLUSION Severe iron deficiency may indicate an increased risk of EO-CRC,particularly at earlier stages.Further studies defining the optimal serum ferritin threshold and routine incorporation of serum ferritin in screening algorithms is essential to develop more effective screening strategies for EO-CRC.
基金supported by grants from the National Natural Science Foundation of China(No.82172983).
文摘Objective Ferritin,initially acting as an iron-storage protein,was found to be associated with metabolic diseases.Our study was designed to investigate the association between serum ferritin and metabolic-associated fatty liver disease(MAFLD)using data from the National Health and Nutrition Examination Survey(NHANES)of the United State of America.Methods A cross-sectional study was conducted,enrolling a total of 2145 participants from the NHANES in the 2017–2018 cycles.Hepatic steatosis and liver fibrosis were assessed by ultrasound images and several non-invasive indexes.Multiple regression analysis was conducted to determine the associations between serum ferritin concentration and MAFLD and liver fibrosis.Results The analysis revealed that participants with higher serum ferritin levels(Q3 and Q4 groups)had a higher prevalence of MAFLD than those with the lowest serum ferritin levels[Q3 vs.Q1:OR=2.17(1.33,3.53),P<0.05 in fatty liver index(FLI);Q4 vs.Q1:OR=3.13(1.91,5.13),P<0.05 in FLI].Additionally,participants with the highest serum ferritin levels(Q4 group)displayed a higher prevalence of liver fibrosis[Q4 vs.Q1:OR=2.59(1.19,5.62),P<0.05 in liver stiffness measurement;OR=5.06(1.12,22.94),P<0.05 in fibrosis-4 index],with significantly increased risk observed in participants with concomitant diabetes[OR=7.45(1.55,35.72),P=0.012].Conclusion Our study revealed that elevated serum ferritin levels are associated with a higher prevalence of MAFLD and advanced liver fibrosis in patients.Elevated serum ferritin levels combined with diabetes are important risk factors for liver fibrosis.
基金Supported by the National Natural Science Foundation of China,No.81471094 and No.82202743.
文摘BACKGROUND Recently,type 2 diabetic osteoporosis(T2DOP)has become a research hotspot for the complications of diabetes,but the specific mechanism of its occurrence and development remains unknown.Ferroptosis caused by iron overload is con-sidered an important cause of T2DOP.Polycytosine RNA-binding protein 1(PCBP1),an iron ion chaperone,is considered a protector of ferroptosis.AIM To investigate the existence of ferroptosis and specific role of PCBP1 in the development of type 2 diabetes.METHODS A cell counting kit-8 assay was used to detect changes in osteoblast viability under high glucose(HG)and/or ferroptosis inhibitors at different concentrations and times.Transmission electron microscopy was used to examine the morpho-logical changes in the mitochondria of osteoblasts under HG,and western blotting was used to detect the expression levels of PCBP1,ferritin,and the ferroptosis-related protein glutathione peroxidase 4(GPX4).A lentivirus silenced and overex-pressed PCBP1.Western blotting was used to detect the expression levels of the osteoblast functional proteins osteoprotegerin(OPG)and osteocalcin(OCN),whereas flow cytometry was used to detect changes in reactive oxygen species(ROS)levels in each group.RESULTS Under HG,the viability of osteoblasts was considerably decreased,the number of mitochondria undergoing atrophy was considerably increased,PCBP1 and ferritin expression levels were increased,and GPX4 expression was decreased.Western blotting results demonstrated that infection with lentivirus overexpressing PCBP1,increased the expression levels of ferritin,GPX4,OPG,and OCN,compared with the HG group.Flow cytometry results showed a reduction in ROS,and an opposite result was obtained after silencing PCBP1.CONCLUSION PCBP1 may protect osteoblasts and reduce the harm caused by ferroptosis by promoting ferritin expression under a HG environment.Moreover,PCBP1 may be a potential therapeutic target for T2DOP.
文摘BACKGROUND Gastric cancer is a kind of malignant tumor which is prevalent all over the world.Although some progress has been made in the treatment of gastric cancer,its prognosis is still not optimistic,so it is of great significance to find reliable prog-nostic indicators to guide the treatment and management of patients with gastric cancer.AIM To explore the relationship between serum levels of five biomarkers[carcinoem-bryonic antigen(CEA),carbohydrate antigen(CA)19-9,CA72-4,CA24-2,and ferritin]and prognosis in patients with gastric cancer.METHODS This study included 200 patients with gastric adenocarcinoma,and conducted an in-depth analysis of their baseline characteristics,relationship between tumor markers and staging,and prognosis.The study found that CA19-9 has a signi-ficant correlation with tumor stage,the average levels of CA24-2,CEA,CA72-4 and ferritin were slightly increased disregarding the stage of tumor.Survival analysis showed that increases in CEA,CA19-9,CA24-2,and ferritin were all associated with shortened overall survival of patients.Further multivariate ana-lysis revealed that elevated serum CA72-4 levels were an inde-pendent adverse prognostic factor.RESULTS This study reveals that there is a significant correlation between the expression levels of serum tumor markers CEA,CA19-9,CA72-4,CA24-2 and ferritin in patients with gastric cancer and prognosis,and can be used as important indicators for prognostic evaluation of gastric cancer.In particular,markers that appear abnormally elevated initially may help identify gastric cancer patients with poor prognosis.CONCLUSION Serum CEA and CA19-9 play an important role in the prognosis assessment of gastric cancer,and are effective tools to guide clinical practice and optimize individualized treatment strategies for gastric cancer patients.
文摘目的利用昆虫细胞/杆状病毒系统表达细粒棘球蚴Eg95-Eg.ferritin融合蛋白,用于开发包虫病新型疫苗以及建立相关血清学诊断方法等研究。方法从细粒棘球蚴包囊中分离原头节,超声粉碎后提取总RNA为模板,通过RT-PCR扩增细粒棘球蚴Eg95和Eg.ferritin基因,采用基因拼接法将Eg95和Eg.ferritin融合,将该融合基因Eg95-Eg.ferritin插入到p Fast Bac DUAL载体中,构建重组转座载体后转化DH10Bac感受态细胞,获得重组Bacmid质粒后转染Sf-9昆虫细胞,传毒3代,对表达蛋白进行Western blot鉴定。结果成功克隆了Eg95和Eg.ferritin基因,通过柔性氨基酸linker成功获得了融合基因Eg95-Eg.ferritin,经PCR和酶切鉴定成功构建了重组质粒p Fast Bac DUAL-Eg95-Eg.ferritin,Western blot结果证实表达蛋白能够被包虫病人标准阳性血清识别。结论在Bac-to-Bac杆状病毒表达系统中成功表达了细粒棘球蚴Eg95-Eg.ferritin融合蛋白,与包虫病人标准阳性血清具有良好的反应性。
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,No.2015R1D1A1A01059980partially supported by the Research Institute for Veterinary Science,Seoul National University
文摘In the present study, we used immunohistochemistry and western blot analysis to examine changes in the levels and cellular localization of iron, heavy chain ferritin（ferritin-H）, and transferrin in the gerbil hippocampal CA1 region from 30 minutes to 7 days following transient forebrain ischemia. Relative to sham controls, iron reactivity increased significantly in the stratum pyramidale and stratum oriens at 12 hours following ischemic insult, transiently decreased at 1–2 days and then increased once again within the CA1 region at 4–7 days after ischemia. One day after ischemia, ferritin-H immunoreactivity increased significantly in the stratum pyramidale and decreased at 2 days. At 4–7 days after ischemia, ferritin-H immunoreactivity in the glial components in the CA1 region was significantly increased. Transferrin immunoreactivity was increased significantly in the stratum pyramidale at 12 hours, peaked at 1 day, and then decreased significantly at 2 days after ischemia. Seven days after ischemia, Transferrin immunoreactivity in the glial cells of the stratum oriens and radiatum was significantly increased. Western blot analyses supported these results, demonstrating that compared to sham controls, ferritin H and transferrin protein levels in hippocampal homogenates significantly increased at 1 day after ischemia, peaked at 4 days and then decreased. These results suggest that iron overload-induced oxidative stress is most prominent at 12 hours after ischemia in the stratum pyramidale, suggesting that this time window may be the optimal period for therapeutic intervention to protect neurons from ischemia-induced death.
基金funded by Shanghai Municipal Health Bureau,No.KPB-WSJ1004the National Natural Science Foundation of China,No.81200971
文摘Iron is an essential trophic element that is required for cell viability and differentiation, especially in oligodendrocytes, which consume relatively high rates of energy to produce myelin. Multiple iron metabolism proteins are expressed in the brain including transferrin receptor and ferritin-H. However, it is still unknown whether they are developmentally regulated in oligodendrocyte lineage cells for myelination. Here, using an in vitro cultured differentiation model of oligodendrocytes, we found that both transferrin receptor and ferritin-H are significantly upregulated during oligodendrocyte maturation, implying the essential role of iron in the development of oligodendrocytes. Additional different doses of Fe3＋ in the cultured medium did not affect oligodendrocyte precursor cell maturation or ferritin-H expression but decreased the expression of the transferrin receptor. These results indicate that upregulation of both transferrin receptor and ferritin-H contributes to maturation and myelination of oligodendrocyte precursor cells.
文摘Background: Iron overload in association with persistent anemia is responsible for endocrine dysfunction in β-thalassemia patients, blood transfusion combined with iron-chelation can modify life quality in these children, but they tend to suffer from delayed maturity and endocrine dysfunction. Aim: This study aims to correlate degree of hypogonadism to ferritin load in regular transfused β-thalassemia patients. Methods: It was carried out on 30 β-thalassemia major (TM) patients aged 12 to 18 years, puberty was assessed clinically, blood picture on Cell-Dyne 2700, ferritin level and pattern of FSH, LH, testosterone and estradiol before and after gonadotropin (GnRH) analogue stimulation test, they were determined on ARCHITECT ABBOTT system. Results: Twenty patients had not yet achieved puberty, FSH level was 1.45 ± 1.88 mIU/ml before (GnRH) analogue and 3.78 ± 4.19 mIU/ml after 4 hours of injection. LH level was 1.91 ± 4.79 mIU/ml before (GnRH) test, while after 4 hours it was 6.52 ± 7.50 mIU/ml, 88.24% of males had low serum testosterone level, 84.6% of girls had low serum estradiol level, FSH, LH, estradiol, testosterone before and after GNRH analogue were statistically insignificant, mean ferritin level was 3344.32 ± 1142.142 ng/ml, with insignificant correlation to hormonal pattern before and after GnRH therapy. Conclusion: Iron overload and hypogonadism are the presenting data in this study, insignificant correlation between ferritin level and hormonal reserve pattern, there may be another etiology in pathophysiology of low gonadal reserve such as severe anemia, chronic disease and may be genetic predisposition underlying susceptibility to iron toxicity, which need further investigations.
基金supported by the National Natural Science Foundation of China,No.81771892(to JHC).
文摘The neuronal differentiation of mesenchymal stem cells offers a new strategy for the treatment of neurological disorders.Thus,there is a need to identify a noninvasive and sensitive in vivo imaging approach for real-time monitoring of transplanted stem cells.Our previous study confirmed that magnetic resonance imaging,with a focus on the ferritin heavy chain 1 reporter gene,could track the proliferation and differentiation of bone marrow mesenchymal stem cells that had been transduced with lentivirus carrying the ferritin heavy chain 1 reporter gene.However,we could not determine whether or when bone marrow mesenchymal stem cells had undergone neuronal differentiation based on changes in the magnetic resonance imaging signal.To solve this problem,we identified a neuron-specific enolase that can be differentially expressed before and after neuronal differentiation in stem cells.In this study,we successfully constructed a lentivirus carrying the neuron-specific enolase promoter and expressing the ferritin heavy chain 1 reporter gene;we used this lentivirus to transduce bone marrow mesenchymal stem cells.Cellular and animal studies showed that the neuron-specific enolase promoter effectively drove the expression of ferritin heavy chain 1 after neuronal differentiation of bone marrow mesenchymal stem cells;this led to intracellular accumulation of iron and corresponding changes in the magnetic resonance imaging signal.In summary,we established an innovative magnetic resonance imaging approach focused on the induction of reporter gene expression by a neuron-specific promoter.This imaging method can be used to noninvasively and sensitively detect neuronal differentiation in stem cells,which may be useful in stem cell-based therapies.
