AIM To develop a non-invasive model to evaluate significant fibrosis and cirrhosis by investigating the association between serum ceruloplasmin(CP) levels and liver fibrosis in chronic hepatitis B(CHB) patients with n...AIM To develop a non-invasive model to evaluate significant fibrosis and cirrhosis by investigating the association between serum ceruloplasmin(CP) levels and liver fibrosis in chronic hepatitis B(CHB) patients with normal or minimally raised alanine aminotransferase(ALT).METHODS Serum samples and liver biopsy were obtained from 193 CHB patients with minimally raised or normal ALT who were randomly divided into a training group(n = 97) and a validation group(n = 96). Liver histology was evaluated by the METAVIR scoring system. Receiver operator characteristic curves were applied to the diagnostic value of CP for measuring liver fibrosis in CHB patients. Spearman rank correlation analyzed the relationship between CP and liver fibrosis. A noninvasive model was set up through multivariate logistic regression analysis.RESULTS Serum CP levels individualized various fibrosis stages via area under the curve(AUC) values. Multivariate analysis revealed that CP levels were significantlyrelated to liver cirrhosis. Combining CP with serum GGT levels, a CG model was set up to predict significant fibrosis and liver cirrhosis in CHB patients with normal or minimally raised ALT. The AUC, sensitivity, specificity, positive predictive value, and negative predictive value were 0.84, 83.1%, 78.6%, 39.6%, and 96.5% to predict liver cirrhosis, and 0.789, 80.26%, 68.38%, 62.25%, and 84.21% to predict significant fibrosis. This model expressed a higher AUC than FIB-4(age, ALT, aspartate aminotransferase, platelets) and GP(globulin, platelets) models to predict significant fibrosis(P = 0.019 and 0.022 respectively) and revealed a dramatically greater AUC than FIB-4(P = 0.033) to predict liver cirrhosis.CONCLUSION The present study showed that CP was independently and negatively associated with liver fibrosis. Furthermore, we developed a novel promising model(CG), based on routine serum markers, for predicting liver fibrosis in CHB patients with normal or minimally raised ALT.展开更多
Safe trafficking of iron across the cell membrane is a delicate process that requires specific protein carriers. While many proteins involved in iron uptake by cells are known, only one cellular iron export protein ha...Safe trafficking of iron across the cell membrane is a delicate process that requires specific protein carriers. While many proteins involved in iron uptake by cells are known, only one cellular iron export protein has been identified in mammals: ferroportin(SLC40A1). Ceruloplasmin is a multicopper enzyme endowed with ferroxidase activity that is found as a soluble isoform in plasma or as a membrane-associated isoform in specific cell types. According to the currently accepted view, ferrous iron transported out of the cell by ferroportin would be safely oxidized by ceruloplasmin to facilitate loading on transferrin. Therefore, the ceruloplasminferroportin system represents the main pathway for cellular iron egress and it is responsible for physiological regulation of cellular iron levels. The most recent findings regarding the structural and functional features of ceruloplasmin and ferroportin and their relationship will be described in this review.展开更多
BACKGROUND The presence of significant liver fibrosis in hepatitis B virus(HBV)-infected individuals with persistently normal serum alanine aminotransferase(PNALT)levels is a strong indicator for initiating antiviral ...BACKGROUND The presence of significant liver fibrosis in hepatitis B virus(HBV)-infected individuals with persistently normal serum alanine aminotransferase(PNALT)levels is a strong indicator for initiating antiviral therapy.Serum ceruloplasmin(CP)is negatively correlated with liver fibrosis in HBV-infected individuals.AIM To examine the potential value of serum CP and develop a noninvasive index including CP to assess significant fibrosis among HBV-infected individuals with PNALT.METHODS Two hundred and seventy-five HBV-infected individuals with PNALT were retrospectively evaluated.The association between CP and fibrotic stages was statistically analyzed.A predictive index including CP[Ceruloplasmin hepatitis B virus(CPHBV)]was constructed to predict significant fibrosis and compared to previously reported models.RESULTS Serum CP had an inverse correlation with liver fibrosis(r=-0.600).Using CP,the areas under the curves(AUCs)to predict significant fibrosis,advanced fibrosis,and cirrhosis were 0.774,0.812,and 0.853,respectively.The CPHBV model was developed using CP,platelets(PLT),and HBsAg levels to predict significant fibrosis.The AUCs of this model to predict significant fibrosis,advanced fibrosis,and cirrhosis were 0.842,0.920,and 0.904,respectively.CPHBV was superior to previous models like the aspartate aminotransferase(AST)-to-PLT ratio index,Fibrosis-4 score,gamma-glutamyl transpeptidase-to-PLT ratio,Forn’s score,and S-index in predicting significant fibrosis in HBV-infected individuals with PNALT.CONCLUSION CPHBV could accurately predict liver fibrosis in HBV-infected individuals with PNALT.Therefore,CPHBV can be a valuable tool for antiviral treatment decisions.展开更多
Objective To explore effects of cerebral ischemia on the ceruloplasmin （Cp） expression in the cortex and hippoc-ampus of rats. Methods Male Wistar rats were randomly divided into cerebral ischemia group and control ...Objective To explore effects of cerebral ischemia on the ceruloplasmin （Cp） expression in the cortex and hippoc-ampus of rats. Methods Male Wistar rats were randomly divided into cerebral ischemia group and control group. Cerebral ischemia was induced by ligating bilateral common carotid arteries and the ischemic rats were further subgrouped according to ischemia time. The control rats received a sham operation. The expression of Cp mRNA in the cortex and hippocampus was measured by reverse transcription polymerase chain reaction （RT-PCR）. The Cp expression was shown by immunohistochemistrical （streptavidin peroxidase, SP） method. Results In ischemia group, the expression of Cp mRNA in the cortex and hippocampus decreased compared with that in control group （P 〈 0.01）; and the longer rats experienced cerebral ischemia, the lower Cp mRNA expressed. By immunohistochemistry, Cp was shown expressed in the neural cells including epithelial cells of choroid plexus, ependymal cells, astrocytes of cortex and hippocampus, and vascular endothelial cells, but not in pyramidal cells and granulosa cells of cortex and hippocampus. Cp levels in the cortex and hippocampus decreased in rats suffering from cerebral ischemia for 3 d, 7 d and 28 d but not in rats exposed to ischemia for 1 d compared with that in control group （P 〈 0.05）. Iron concentration correlated negatively with Cp expression in the cortex and hippocampus of rats exposure to ischemia （the cortex, r=-0.831, P〈0.01; the hippocampus, r=-0.809, P〈0.01）. Conclusion Cerebral ischemia inhibited Cp expression in the cortex and hippocampus of rats. The decrease of Cp might be involved in iron deposition in neurons.展开更多
Human α1(Ⅰ), α2(Ⅰ) and α1(Ⅲ) cDNA probes and RNA dot hybridization were employed to quantitate collagen mRNA changes after adding silica dust into the media of human 2BS fibroblasts. At all dosages used (100, 20...Human α1(Ⅰ), α2(Ⅰ) and α1(Ⅲ) cDNA probes and RNA dot hybridization were employed to quantitate collagen mRNA changes after adding silica dust into the media of human 2BS fibroblasts. At all dosages used (100, 200, 500 and 1000μg), the α1(Ⅰ), α2(Ⅰ)and α1(Ⅲ) mRNA levels increased one day after dusting. At the same dosage of silica (100μg), α1(Ⅲ) mRNA increased earlier than type Ⅰ collagen mRNA did. The type Ⅰ and type Ⅲ collagen mRNA contents in the experimental groups were higher than those in control on days 3, 5, 7 and 9. The effect of ceruloplasmin (Cp) and fibronectin (Fn) on collagen mRNA synthesis was also studied, after adding silica dust, Cp or Fn into the media of human 2BS fibroblast. The results showed that Cp and Fn have stimulating effect on collagen mRNA production. When both Cp and silica dust were added into cell culture media, the collagen mRNA level was increased more than those of adding either Cp or silica dust alone. Similar situations were found for Fn. Cp (or Fn) synergism with silica dust on stimulating transcription of human collagen gene was suggested展开更多
Periodontitis, is an infectious ailment of multifactorial origin, that brings about destruction of bone and surrounding tissues. There are various oral pathogens that may be responsible for the destruction. The host e...Periodontitis, is an infectious ailment of multifactorial origin, that brings about destruction of bone and surrounding tissues. There are various oral pathogens that may be responsible for the destruction. The host encounters these microbial invasions and their products by the production and release of inflammatory mediators from the cells within the body. Glutathione-S-transferase (GST) are a group of enzymes that utilize glutathione in conditions resulting in oxidative stress. These enzymes play a key role in the detoxifycation of such substance. It aids in preventing damage to important cellular components caused by release of free reactive oxygen species. Ceruloplasmin is a ferroxidase enzyme. It plays a role as an anti-inflammatory agent, by its ability to scavenge free radicals within the body. The present study was targeted at evaluating the levels of Glutathione-S-Transferase (GST) and Ceruloplasmin as diagnostic markers for patients with chronic periodontitis in gingival crevicular fluid (GCF) and the gingival tissues. Thirty patients were divided into two groups. Experimental group comprising of 15 subjects with chronic perio- dontitis and the control group was composed of 15 healthy individuals. Highly significant changes in GST between the diseased and normal patients (P = 0.001) were detected. There was a decrease in GST level in both gingival tissue & GCF in diseased patients when compared to the control patients. The ceruloplasmin levels in GCF and gingival tissues showed no difference between the control and diseased group. Hence,these results indicate a relationship suggesting that GST produced during chronic inflammation could be used as biomarker that indicate periodontal disease .展开更多
Background: Ceruloplasmin is an acute phase protein with plasma copper binding properties, and is a potent extracellular antioxidative enzyme. Inflammation and oxidative stress might explain the role of ceruloplasmin ...Background: Ceruloplasmin is an acute phase protein with plasma copper binding properties, and is a potent extracellular antioxidative enzyme. Inflammation and oxidative stress might explain the role of ceruloplasmin in the pathophysiology of heart failure. Study objective: The objective is to assess the correlation of ceruloplasmin levels with biomarkers of cardiac remodelling and myofibrosis in patients with acute decompensated heart failure. Patients and methods: Blood samples were taken and serum levels of soluble ST2, galectin-3, NT-proBNP and ceruloplasmin were analysed in 31 consecutive patients with systolic HF referred to tertiary care nurse lead heart failure clinic with acute decompensated CHF requiring i.v. diuretics. The mean patients’ age was 68 years, mean left ventricular ejection fraction (LV EF) was 29%, 66% patients had ischemic aetilogy of CHF and 33% had atrial fibrillation. Results: The mean ceruloplasmin level was 0.243 g/l, mean galectin-3 level was 1.26 ng/ml, mean sST2 level was 38.15 ng/ml, and mean NT-proBNP was 1927 pg/ml. The ceruloplasmin level correlated with NT-proBNP (r = 0.58, p < 0.05) and with sST2 (r = 0.77, p < 0.001), sST2 levels correlated significantly with NT-proBNP (r = 0.66, p < 0.01). The ceruloplasmin level did not correlate with galectin-3 concentration. Conclusion: The ceruloplasmin level correlates with the biomarkers of cardiac remodelling (NT-proBNP, sST2), but not with the biomarker of myofibrosis (galectin-3). This finding supports the hypothesis of inflammatory response in acute decompensated heart failure.展开更多
Ceruloplasmin (CP) in peripheral leucocytes was determined by radioimmunoassay.It was observed that leucocytes of normal persons and leukemic patients contained CP. TheCP contents of polymorphonuclear cells (PMN) and ...Ceruloplasmin (CP) in peripheral leucocytes was determined by radioimmunoassay.It was observed that leucocytes of normal persons and leukemic patients contained CP. TheCP contents of polymorphonuclear cells (PMN) and blast cells of acute leukemia not in re-mission were both significantly higher than that of normal (P【0.05) and than that of acuteleukemia complete remission (P【0.05).展开更多
Serum ceruloplasmin (CP) was determined by electroimmunodiffusion method in 89 normal persons and 92 leukemic patients. It was found that the serum CP of acute and chronic leukemia was very significantly higher than n...Serum ceruloplasmin (CP) was determined by electroimmunodiffusion method in 89 normal persons and 92 leukemic patients. It was found that the serum CP of acute and chronic leukemia was very significantly higher than normal (P【0.01). There were no signifcant difference in elevation of serum CP between various types of leukemia. During remission oJ acute or chronic leukemia, the serum CP decreased significantly (P【0.05), but still higher than normal (P【0.01). In the case of long-term remission, serum CP decreased to normal level. During relapse of acute leukemia or acute blast crisis of chronic leukemia, serum CP raised again significantly (P【0.05). Infection enabled the leukemic patient to further increase serum CP (P【0.01). In acute leukemia, serum CP level correlated positively with the percentage of blast cells in bone marrow (P【0.05).展开更多
Ceruloplasmin (Cp), a copper metalloprotein in human serum has been a valuable diagnostic marker in Wilson’s disease where Cp levels tend to be low while high levels in serum were asso-ciated with myocardial infarcti...Ceruloplasmin (Cp), a copper metalloprotein in human serum has been a valuable diagnostic marker in Wilson’s disease where Cp levels tend to be low while high levels in serum were asso-ciated with myocardial infarction, neoplastic and inflammatory conditions. There is no stan-dardized reference method for Cp and current immunologic and bichromatic assays have a number of drawbacks. The method described here uses immunoaffinity chromatography to remove six of the most abundant proteins from a serum sample and high-pressure liquid chro- matography (HPLC) with a size-exclusion col-umn to separate Cp from other serum proteins and any free Cu prior to analysis of 63Cu and 65Cu by inductively-coupled plasma mass spec-trometry (ICPMS). Identification of Cp is based on retention time match of the unknown protein in the serum sample with the Cp external stan-dard and the presence of 63Cu and 65Cu at a ratio of 2.2 ± 0.1. The method accuracy, as estab-lished independently by two of the authors with a reference serum certified for Cp, is 98 to 101% and the coefficient of variation is 6.4% and 5.4%, respectively. The assay was used to analyze a total of 167 human sera for Cp from patients with myocardial infarction (MI), pulmonary em-bolism (PE), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), other forms of ar-thritis, and a set of healthy patients as normal controls (NC). Our data show that Cp concen-trations tend to be higher in MI, RA, and SLE patients, higher in female as compared to male patients, and we did not observe a correlation between Cp concentration and patient’s age for the set of 70 patients for which we had gender and age information.展开更多
Purpose: The study aimed at evaluation of the role of ceruloplasmin (A protein involved in iron homeostasis and can inactivate free radicals) and other oxidative stress markers as superoxide dismutase (SOD), malondial...Purpose: The study aimed at evaluation of the role of ceruloplasmin (A protein involved in iron homeostasis and can inactivate free radicals) and other oxidative stress markers as superoxide dismutase (SOD), malondialdehyde (MDA) and catalase activity (CAT) in primary open angle glaucoma (POAG). Methods: This observational case control study included 90 persons divided into 3 equal groups: group A of 30 normal persons as a control group, group B of 30 patients of untreated (POAG) (firstly diagnosed) by the clinical characters including measuring intraocular pressure (IOP), optic disc cupping and visual field changes and group C of 30 patients of POAG under medical treatment by topical anti-glaucomatous drugs. Serum ceruloplasmin, superoxide dismutase, malondialdehyde and catalase activity were measured in all groups, statistical analysis of the data was performed. Results: In a comparison to group A of control, serum ceruloplasmin decreased significantly in group B of untreated POAG (20.95 ± 6.01) mg-dl and in group C of POAG under treatment (22.15 ± 6.14) mg-dl (P 0.05). Also, serum superoxide dismutase increased significantly in group B (2.23 ± 0.4) and in group C (2.19 ± 0.38) U-ml (P 0.05). Serum malondialdehyde increased significantly in group B (3.82 ± 0.74) nmol-ml and in group C (3.55 ± 0.73) nmol-ml (P 0.05). Serum catalase decreased significantly in group B (17.97 ± 2.75) U-ml and in group C (18.75 ± 2.33) U-ml in a comparison to the control group A (22.67 ± 3.05) U-ml (P 0.05). Conclusions: Serum ceruloplasmin level and the antioxidant (CAT) activity significantly decreased, while serum levels of SOD, MDA significantly increased in cases of POAG. This may indicate the need for addition of anti-oxidative stress therapy in combination with the anti-glaucomatous drugs. Monitoring these markers can be considered good indicators for determination of the oxidative stress condition in such cases.展开更多
Objective:Bilirubin is a double edged sword in biological system,acting as a toxic molecule and cytoprotectant.Unconjugated bilirubin is proved to show antioxidant activity in vitro and in vivo.In the current work we ...Objective:Bilirubin is a double edged sword in biological system,acting as a toxic molecule and cytoprotectant.Unconjugated bilirubin is proved to show antioxidant activity in vitro and in vivo.In the current work we tried to know the relationship between both conjugated and unconjugated bilirubin with copper and protein thiols in patients with hyperbilirubinemia.Methods:Study was conducted on 56 hyperbilirubinemic cases and 56 healthy controls.Serum copper,ceruloplasmin,protein thiols,total bilirubin,conjugated and unconjugated bilirubin,unconjugated bilirubin/albumin ratio,total protein,albumin,AST,ALT and ALP were estimated.Results:There was significant increase in serum copper,total bilirubin,conjugated and unconjugated bilirubin,unconjugated bilirubin/albumin ratio,AST,ALT,and ALP,and decrease in serum ceruloplasmin,protein thiols,total protein,and albumin in hyperbilirubinemic cases when compared to healthy controls.Conjugated bilirubin correlated positively with liver enzymes AST and ALP,and negatively with protein thiols,total protein and albumin.Unconjugated bilirubin correlated positively with ALT.Protein thiols correlated negatively with copper and positively with ceruloplasmin,and also correlated negatively with liver enzymes like AST,ALT and ALP,and positively with total protein and albumin.Conclusion:Combination of elevated levels of trace elements like copper and availability of reducing agent like bilirubin may prove deleterious by generating free radicals.展开更多
Objective:Ceruloplasmin(CP),a key human ferroxidase,can maintain the iron balance in the brain,and the familial hypoceruloplasminemia might be rare.Ceruloplasmin reduction is one of the most common features in Wilson&...Objective:Ceruloplasmin(CP),a key human ferroxidase,can maintain the iron balance in the brain,and the familial hypoceruloplasminemia might be rare.Ceruloplasmin reduction is one of the most common features in Wilson's disease.Some patients with hypoceruloplasminemia do not fulfill the criteria for the diagnosis of Wilson's disease or other known diseases.Moreover,these patients always suffer from various degrees of abnormal brain iron deposition.We sought to investigate the genetic basis of nonWilson's disease hypoceruloplasminemia using whole-exome sequencing.Methods:We recruited four patients with non-Wilson's disease hypoceruloplasminemia,who visited the Department of Neurology,Shanghai First People's Hospital,China from December 2010 to February 2011.Three of them were from the same pedigree,and the other patient shared no blood relation with the others.Iron deposition in the brain was assessed using quantitative susceptibility mapping and peripheral blood DNA was extracted.The part of the exons'genome were sequenced using the NimbleGen Sequence Capture Array and high-throughput sequencing technologies.Intersection analysis at the single nucleotide polymorphism(SNP)loci was carried out.The selected loci were verified with Sanger sequencing.Results:Magnetic resonance imaging revealed that the magnetic susceptibility in the globus pallidus,which showed with a high signal intensity,was apparently higher in three patients than that in the normal controls,indicating the presence of abnormal iron deposition in the brain.The whole-exome sequencing and Sanger sequencing primarily excluded the possibility of mutations in the CP,ATP7B,and ATP7A genes that may impact ceruloplasmin levels.The four patients presented the homozygous mutation c.3611A>C in the C12orf51 gene;this was suspected to be a causative mutation after excluding SNP loci that were the same as those in the common population,as per The 1000 Genomes Project.Conclusion:Non-Wilson's disease hypoceruloplasminemia showed varying degrees of abnormal iron deposition in the brain,and was possibly associated with the c.3611A>C mutation in C12orf51.How copper and iron regulate the levels of one another in the body is still not fully understood.The reduction of ceruloplasmin levels and brain iron deposition probably participated in the occurrence and development of neurodegenerative diseases.Following the combination of pre-existing techniques with a new generation of gene sequencing,the early diagnosis,prevention,and treatment of non-Wilson's disease hypoceruloplasminemia and other neurodegenerative diseases can be achieved.展开更多
We are writing in response to“Brain iron deposition and wholeexome sequencing of non-Wilson's disease hypoceruloplasminemia in a family”by Dr.Wang and colleagues.1 We found the article very thought-provoking,and...We are writing in response to“Brain iron deposition and wholeexome sequencing of non-Wilson's disease hypoceruloplasminemia in a family”by Dr.Wang and colleagues.1 We found the article very thought-provoking,and believe that Dr.Wang's team may be on the verge of discovering a new disease spectrum.This novel disease is characterized by the following features:low serum ceruloplasmin,age-related brain iron accumulation,and a homozygous c.3611A>C mutation in C12orf51.展开更多
Nonalcoholic steatohepatitis(NASH)is a condition that progresses from nonalcoholic fatty liver disease(NAFLD)and is characterized by hepatic fat accumulation,inflammation,and fibrosis.It has the potential to develop i...Nonalcoholic steatohepatitis(NASH)is a condition that progresses from nonalcoholic fatty liver disease(NAFLD)and is characterized by hepatic fat accumulation,inflammation,and fibrosis.It has the potential to develop into cirrhosis and liver cancer,and currently no effective pharmacological treatment is available.In this study,we investigate the therapeutic potential of targeting ceruloplasmin(Cp),a copper-containing protein predominantly secreted by hepatocytes,for treating NASH.Our result show that hepatic Cp is remarkedly upregulated in individuals with NASH and the mouse NASH model.Hepatocyte-specific Cp ablation effectively attenuates the onset of dietary-induced NASH by decreasing lipid accumulation,curbing inflammation,mitigating fibrosis,and ameliorating liver damage.By employing transcriptomics and metabolomics approaches,we have discovered that hepatic deletion of Cp brings about remarkable restoration of bile acid(BA)metabolism during NASH.Hepatic deletion of Cp effectively remodels BA metabolism by upregulating Cyp7a1 and Cyp8b1,which subsequently leads to enhanced BA synthesis and notable alterations in BA profiles.In conclusion,our studies elucidate the crucial involvement of Cp in NASH,highlighting its significance as a promising therapeutic target for the treatment of this disease.展开更多
基金Supported by Youth Foundation of the Health and Family Planning Commission of Fujian Province,No.2014-1-55
文摘AIM To develop a non-invasive model to evaluate significant fibrosis and cirrhosis by investigating the association between serum ceruloplasmin(CP) levels and liver fibrosis in chronic hepatitis B(CHB) patients with normal or minimally raised alanine aminotransferase(ALT).METHODS Serum samples and liver biopsy were obtained from 193 CHB patients with minimally raised or normal ALT who were randomly divided into a training group(n = 97) and a validation group(n = 96). Liver histology was evaluated by the METAVIR scoring system. Receiver operator characteristic curves were applied to the diagnostic value of CP for measuring liver fibrosis in CHB patients. Spearman rank correlation analyzed the relationship between CP and liver fibrosis. A noninvasive model was set up through multivariate logistic regression analysis.RESULTS Serum CP levels individualized various fibrosis stages via area under the curve(AUC) values. Multivariate analysis revealed that CP levels were significantlyrelated to liver cirrhosis. Combining CP with serum GGT levels, a CG model was set up to predict significant fibrosis and liver cirrhosis in CHB patients with normal or minimally raised ALT. The AUC, sensitivity, specificity, positive predictive value, and negative predictive value were 0.84, 83.1%, 78.6%, 39.6%, and 96.5% to predict liver cirrhosis, and 0.789, 80.26%, 68.38%, 62.25%, and 84.21% to predict significant fibrosis. This model expressed a higher AUC than FIB-4(age, ALT, aspartate aminotransferase, platelets) and GP(globulin, platelets) models to predict significant fibrosis(P = 0.019 and 0.022 respectively) and revealed a dramatically greater AUC than FIB-4(P = 0.033) to predict liver cirrhosis.CONCLUSION The present study showed that CP was independently and negatively associated with liver fibrosis. Furthermore, we developed a novel promising model(CG), based on routine serum markers, for predicting liver fibrosis in CHB patients with normal or minimally raised ALT.
文摘Safe trafficking of iron across the cell membrane is a delicate process that requires specific protein carriers. While many proteins involved in iron uptake by cells are known, only one cellular iron export protein has been identified in mammals: ferroportin(SLC40A1). Ceruloplasmin is a multicopper enzyme endowed with ferroxidase activity that is found as a soluble isoform in plasma or as a membrane-associated isoform in specific cell types. According to the currently accepted view, ferrous iron transported out of the cell by ferroportin would be safely oxidized by ceruloplasmin to facilitate loading on transferrin. Therefore, the ceruloplasminferroportin system represents the main pathway for cellular iron egress and it is responsible for physiological regulation of cellular iron levels. The most recent findings regarding the structural and functional features of ceruloplasmin and ferroportin and their relationship will be described in this review.
基金the Science and Technology Department of Fujian Province,No.2018J01164Quanzhou Science and Technology Bureau Planning Project,No.2019N019S.
文摘BACKGROUND The presence of significant liver fibrosis in hepatitis B virus(HBV)-infected individuals with persistently normal serum alanine aminotransferase(PNALT)levels is a strong indicator for initiating antiviral therapy.Serum ceruloplasmin(CP)is negatively correlated with liver fibrosis in HBV-infected individuals.AIM To examine the potential value of serum CP and develop a noninvasive index including CP to assess significant fibrosis among HBV-infected individuals with PNALT.METHODS Two hundred and seventy-five HBV-infected individuals with PNALT were retrospectively evaluated.The association between CP and fibrotic stages was statistically analyzed.A predictive index including CP[Ceruloplasmin hepatitis B virus(CPHBV)]was constructed to predict significant fibrosis and compared to previously reported models.RESULTS Serum CP had an inverse correlation with liver fibrosis(r=-0.600).Using CP,the areas under the curves(AUCs)to predict significant fibrosis,advanced fibrosis,and cirrhosis were 0.774,0.812,and 0.853,respectively.The CPHBV model was developed using CP,platelets(PLT),and HBsAg levels to predict significant fibrosis.The AUCs of this model to predict significant fibrosis,advanced fibrosis,and cirrhosis were 0.842,0.920,and 0.904,respectively.CPHBV was superior to previous models like the aspartate aminotransferase(AST)-to-PLT ratio index,Fibrosis-4 score,gamma-glutamyl transpeptidase-to-PLT ratio,Forn’s score,and S-index in predicting significant fibrosis in HBV-infected individuals with PNALT.CONCLUSION CPHBV could accurately predict liver fibrosis in HBV-infected individuals with PNALT.Therefore,CPHBV can be a valuable tool for antiviral treatment decisions.
文摘Objective To explore effects of cerebral ischemia on the ceruloplasmin （Cp） expression in the cortex and hippoc-ampus of rats. Methods Male Wistar rats were randomly divided into cerebral ischemia group and control group. Cerebral ischemia was induced by ligating bilateral common carotid arteries and the ischemic rats were further subgrouped according to ischemia time. The control rats received a sham operation. The expression of Cp mRNA in the cortex and hippocampus was measured by reverse transcription polymerase chain reaction （RT-PCR）. The Cp expression was shown by immunohistochemistrical （streptavidin peroxidase, SP） method. Results In ischemia group, the expression of Cp mRNA in the cortex and hippocampus decreased compared with that in control group （P 〈 0.01）; and the longer rats experienced cerebral ischemia, the lower Cp mRNA expressed. By immunohistochemistry, Cp was shown expressed in the neural cells including epithelial cells of choroid plexus, ependymal cells, astrocytes of cortex and hippocampus, and vascular endothelial cells, but not in pyramidal cells and granulosa cells of cortex and hippocampus. Cp levels in the cortex and hippocampus decreased in rats suffering from cerebral ischemia for 3 d, 7 d and 28 d but not in rats exposed to ischemia for 1 d compared with that in control group （P 〈 0.05）. Iron concentration correlated negatively with Cp expression in the cortex and hippocampus of rats exposure to ischemia （the cortex, r=-0.831, P〈0.01; the hippocampus, r=-0.809, P〈0.01）. Conclusion Cerebral ischemia inhibited Cp expression in the cortex and hippocampus of rats. The decrease of Cp might be involved in iron deposition in neurons.
文摘Human α1(Ⅰ), α2(Ⅰ) and α1(Ⅲ) cDNA probes and RNA dot hybridization were employed to quantitate collagen mRNA changes after adding silica dust into the media of human 2BS fibroblasts. At all dosages used (100, 200, 500 and 1000μg), the α1(Ⅰ), α2(Ⅰ)and α1(Ⅲ) mRNA levels increased one day after dusting. At the same dosage of silica (100μg), α1(Ⅲ) mRNA increased earlier than type Ⅰ collagen mRNA did. The type Ⅰ and type Ⅲ collagen mRNA contents in the experimental groups were higher than those in control on days 3, 5, 7 and 9. The effect of ceruloplasmin (Cp) and fibronectin (Fn) on collagen mRNA synthesis was also studied, after adding silica dust, Cp or Fn into the media of human 2BS fibroblast. The results showed that Cp and Fn have stimulating effect on collagen mRNA production. When both Cp and silica dust were added into cell culture media, the collagen mRNA level was increased more than those of adding either Cp or silica dust alone. Similar situations were found for Fn. Cp (or Fn) synergism with silica dust on stimulating transcription of human collagen gene was suggested
文摘Periodontitis, is an infectious ailment of multifactorial origin, that brings about destruction of bone and surrounding tissues. There are various oral pathogens that may be responsible for the destruction. The host encounters these microbial invasions and their products by the production and release of inflammatory mediators from the cells within the body. Glutathione-S-transferase (GST) are a group of enzymes that utilize glutathione in conditions resulting in oxidative stress. These enzymes play a key role in the detoxifycation of such substance. It aids in preventing damage to important cellular components caused by release of free reactive oxygen species. Ceruloplasmin is a ferroxidase enzyme. It plays a role as an anti-inflammatory agent, by its ability to scavenge free radicals within the body. The present study was targeted at evaluating the levels of Glutathione-S-Transferase (GST) and Ceruloplasmin as diagnostic markers for patients with chronic periodontitis in gingival crevicular fluid (GCF) and the gingival tissues. Thirty patients were divided into two groups. Experimental group comprising of 15 subjects with chronic perio- dontitis and the control group was composed of 15 healthy individuals. Highly significant changes in GST between the diseased and normal patients (P = 0.001) were detected. There was a decrease in GST level in both gingival tissue & GCF in diseased patients when compared to the control patients. The ceruloplasmin levels in GCF and gingival tissues showed no difference between the control and diseased group. Hence,these results indicate a relationship suggesting that GST produced during chronic inflammation could be used as biomarker that indicate periodontal disease .
基金supported by institutional grant Na Homolce Hospital,Prague,Czech Republic IG 140505.
文摘Background: Ceruloplasmin is an acute phase protein with plasma copper binding properties, and is a potent extracellular antioxidative enzyme. Inflammation and oxidative stress might explain the role of ceruloplasmin in the pathophysiology of heart failure. Study objective: The objective is to assess the correlation of ceruloplasmin levels with biomarkers of cardiac remodelling and myofibrosis in patients with acute decompensated heart failure. Patients and methods: Blood samples were taken and serum levels of soluble ST2, galectin-3, NT-proBNP and ceruloplasmin were analysed in 31 consecutive patients with systolic HF referred to tertiary care nurse lead heart failure clinic with acute decompensated CHF requiring i.v. diuretics. The mean patients’ age was 68 years, mean left ventricular ejection fraction (LV EF) was 29%, 66% patients had ischemic aetilogy of CHF and 33% had atrial fibrillation. Results: The mean ceruloplasmin level was 0.243 g/l, mean galectin-3 level was 1.26 ng/ml, mean sST2 level was 38.15 ng/ml, and mean NT-proBNP was 1927 pg/ml. The ceruloplasmin level correlated with NT-proBNP (r = 0.58, p < 0.05) and with sST2 (r = 0.77, p < 0.001), sST2 levels correlated significantly with NT-proBNP (r = 0.66, p < 0.01). The ceruloplasmin level did not correlate with galectin-3 concentration. Conclusion: The ceruloplasmin level correlates with the biomarkers of cardiac remodelling (NT-proBNP, sST2), but not with the biomarker of myofibrosis (galectin-3). This finding supports the hypothesis of inflammatory response in acute decompensated heart failure.
文摘Ceruloplasmin (CP) in peripheral leucocytes was determined by radioimmunoassay.It was observed that leucocytes of normal persons and leukemic patients contained CP. TheCP contents of polymorphonuclear cells (PMN) and blast cells of acute leukemia not in re-mission were both significantly higher than that of normal (P【0.05) and than that of acuteleukemia complete remission (P【0.05).
文摘Serum ceruloplasmin (CP) was determined by electroimmunodiffusion method in 89 normal persons and 92 leukemic patients. It was found that the serum CP of acute and chronic leukemia was very significantly higher than normal (P【0.01). There were no signifcant difference in elevation of serum CP between various types of leukemia. During remission oJ acute or chronic leukemia, the serum CP decreased significantly (P【0.05), but still higher than normal (P【0.01). In the case of long-term remission, serum CP decreased to normal level. During relapse of acute leukemia or acute blast crisis of chronic leukemia, serum CP raised again significantly (P【0.05). Infection enabled the leukemic patient to further increase serum CP (P【0.01). In acute leukemia, serum CP level correlated positively with the percentage of blast cells in bone marrow (P【0.05).
文摘Ceruloplasmin (Cp), a copper metalloprotein in human serum has been a valuable diagnostic marker in Wilson’s disease where Cp levels tend to be low while high levels in serum were asso-ciated with myocardial infarction, neoplastic and inflammatory conditions. There is no stan-dardized reference method for Cp and current immunologic and bichromatic assays have a number of drawbacks. The method described here uses immunoaffinity chromatography to remove six of the most abundant proteins from a serum sample and high-pressure liquid chro- matography (HPLC) with a size-exclusion col-umn to separate Cp from other serum proteins and any free Cu prior to analysis of 63Cu and 65Cu by inductively-coupled plasma mass spec-trometry (ICPMS). Identification of Cp is based on retention time match of the unknown protein in the serum sample with the Cp external stan-dard and the presence of 63Cu and 65Cu at a ratio of 2.2 ± 0.1. The method accuracy, as estab-lished independently by two of the authors with a reference serum certified for Cp, is 98 to 101% and the coefficient of variation is 6.4% and 5.4%, respectively. The assay was used to analyze a total of 167 human sera for Cp from patients with myocardial infarction (MI), pulmonary em-bolism (PE), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), other forms of ar-thritis, and a set of healthy patients as normal controls (NC). Our data show that Cp concen-trations tend to be higher in MI, RA, and SLE patients, higher in female as compared to male patients, and we did not observe a correlation between Cp concentration and patient’s age for the set of 70 patients for which we had gender and age information.
文摘Purpose: The study aimed at evaluation of the role of ceruloplasmin (A protein involved in iron homeostasis and can inactivate free radicals) and other oxidative stress markers as superoxide dismutase (SOD), malondialdehyde (MDA) and catalase activity (CAT) in primary open angle glaucoma (POAG). Methods: This observational case control study included 90 persons divided into 3 equal groups: group A of 30 normal persons as a control group, group B of 30 patients of untreated (POAG) (firstly diagnosed) by the clinical characters including measuring intraocular pressure (IOP), optic disc cupping and visual field changes and group C of 30 patients of POAG under medical treatment by topical anti-glaucomatous drugs. Serum ceruloplasmin, superoxide dismutase, malondialdehyde and catalase activity were measured in all groups, statistical analysis of the data was performed. Results: In a comparison to group A of control, serum ceruloplasmin decreased significantly in group B of untreated POAG (20.95 ± 6.01) mg-dl and in group C of POAG under treatment (22.15 ± 6.14) mg-dl (P 0.05). Also, serum superoxide dismutase increased significantly in group B (2.23 ± 0.4) and in group C (2.19 ± 0.38) U-ml (P 0.05). Serum malondialdehyde increased significantly in group B (3.82 ± 0.74) nmol-ml and in group C (3.55 ± 0.73) nmol-ml (P 0.05). Serum catalase decreased significantly in group B (17.97 ± 2.75) U-ml and in group C (18.75 ± 2.33) U-ml in a comparison to the control group A (22.67 ± 3.05) U-ml (P 0.05). Conclusions: Serum ceruloplasmin level and the antioxidant (CAT) activity significantly decreased, while serum levels of SOD, MDA significantly increased in cases of POAG. This may indicate the need for addition of anti-oxidative stress therapy in combination with the anti-glaucomatous drugs. Monitoring these markers can be considered good indicators for determination of the oxidative stress condition in such cases.
文摘Objective:Bilirubin is a double edged sword in biological system,acting as a toxic molecule and cytoprotectant.Unconjugated bilirubin is proved to show antioxidant activity in vitro and in vivo.In the current work we tried to know the relationship between both conjugated and unconjugated bilirubin with copper and protein thiols in patients with hyperbilirubinemia.Methods:Study was conducted on 56 hyperbilirubinemic cases and 56 healthy controls.Serum copper,ceruloplasmin,protein thiols,total bilirubin,conjugated and unconjugated bilirubin,unconjugated bilirubin/albumin ratio,total protein,albumin,AST,ALT and ALP were estimated.Results:There was significant increase in serum copper,total bilirubin,conjugated and unconjugated bilirubin,unconjugated bilirubin/albumin ratio,AST,ALT,and ALP,and decrease in serum ceruloplasmin,protein thiols,total protein,and albumin in hyperbilirubinemic cases when compared to healthy controls.Conjugated bilirubin correlated positively with liver enzymes AST and ALP,and negatively with protein thiols,total protein and albumin.Unconjugated bilirubin correlated positively with ALT.Protein thiols correlated negatively with copper and positively with ceruloplasmin,and also correlated negatively with liver enzymes like AST,ALT and ALP,and positively with total protein and albumin.Conclusion:Combination of elevated levels of trace elements like copper and availability of reducing agent like bilirubin may prove deleterious by generating free radicals.
基金upported by the National Natural Science Foundation of China(Grant Nos.81071065 and 81671103 to WXP)Shanghai Jiao Tong University School of Medicine’s Brain Innovative Plan 2015。
文摘Objective:Ceruloplasmin(CP),a key human ferroxidase,can maintain the iron balance in the brain,and the familial hypoceruloplasminemia might be rare.Ceruloplasmin reduction is one of the most common features in Wilson's disease.Some patients with hypoceruloplasminemia do not fulfill the criteria for the diagnosis of Wilson's disease or other known diseases.Moreover,these patients always suffer from various degrees of abnormal brain iron deposition.We sought to investigate the genetic basis of nonWilson's disease hypoceruloplasminemia using whole-exome sequencing.Methods:We recruited four patients with non-Wilson's disease hypoceruloplasminemia,who visited the Department of Neurology,Shanghai First People's Hospital,China from December 2010 to February 2011.Three of them were from the same pedigree,and the other patient shared no blood relation with the others.Iron deposition in the brain was assessed using quantitative susceptibility mapping and peripheral blood DNA was extracted.The part of the exons'genome were sequenced using the NimbleGen Sequence Capture Array and high-throughput sequencing technologies.Intersection analysis at the single nucleotide polymorphism(SNP)loci was carried out.The selected loci were verified with Sanger sequencing.Results:Magnetic resonance imaging revealed that the magnetic susceptibility in the globus pallidus,which showed with a high signal intensity,was apparently higher in three patients than that in the normal controls,indicating the presence of abnormal iron deposition in the brain.The whole-exome sequencing and Sanger sequencing primarily excluded the possibility of mutations in the CP,ATP7B,and ATP7A genes that may impact ceruloplasmin levels.The four patients presented the homozygous mutation c.3611A>C in the C12orf51 gene;this was suspected to be a causative mutation after excluding SNP loci that were the same as those in the common population,as per The 1000 Genomes Project.Conclusion:Non-Wilson's disease hypoceruloplasminemia showed varying degrees of abnormal iron deposition in the brain,and was possibly associated with the c.3611A>C mutation in C12orf51.How copper and iron regulate the levels of one another in the body is still not fully understood.The reduction of ceruloplasmin levels and brain iron deposition probably participated in the occurrence and development of neurodegenerative diseases.Following the combination of pre-existing techniques with a new generation of gene sequencing,the early diagnosis,prevention,and treatment of non-Wilson's disease hypoceruloplasminemia and other neurodegenerative diseases can be achieved.
基金the National Natural Science Foundation of China,grant number 82201572the Clinical Medicine Discipline Construction Project of the Putuo District Health Commission,grant number 2023tszb04.
文摘We are writing in response to“Brain iron deposition and wholeexome sequencing of non-Wilson's disease hypoceruloplasminemia in a family”by Dr.Wang and colleagues.1 We found the article very thought-provoking,and believe that Dr.Wang's team may be on the verge of discovering a new disease spectrum.This novel disease is characterized by the following features:low serum ceruloplasmin,age-related brain iron accumulation,and a homozygous c.3611A>C mutation in C12orf51.
基金supported by grants to S.C.from the National Natural Science Foundation of China(82170863)Shanghai Rising-Star Program(21QA1407000),the Lingang Laboratory Grant(LG-QS-202205-06)+5 种基金the Innovative Research Team of High-level Local Universities in Shanghai(SHSMU-ZDCX20212501)Shanghai Sixth People’s Hospital(ynyq202103)supported by grants to J.L.from the National Key R&D Program of China(2021YFA0804800 and 2018YFA0800600)Shanghai Municipal Commission of Science and Technology(20410713200 and 21S11909000)the National Facility for Translational Medicine(TMSK-2020-102)the‘Shuguang Program’supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission(20SG10),and Shanghai Sixth People’s Hospital(ynjq202102).
文摘Nonalcoholic steatohepatitis(NASH)is a condition that progresses from nonalcoholic fatty liver disease(NAFLD)and is characterized by hepatic fat accumulation,inflammation,and fibrosis.It has the potential to develop into cirrhosis and liver cancer,and currently no effective pharmacological treatment is available.In this study,we investigate the therapeutic potential of targeting ceruloplasmin(Cp),a copper-containing protein predominantly secreted by hepatocytes,for treating NASH.Our result show that hepatic Cp is remarkedly upregulated in individuals with NASH and the mouse NASH model.Hepatocyte-specific Cp ablation effectively attenuates the onset of dietary-induced NASH by decreasing lipid accumulation,curbing inflammation,mitigating fibrosis,and ameliorating liver damage.By employing transcriptomics and metabolomics approaches,we have discovered that hepatic deletion of Cp brings about remarkable restoration of bile acid(BA)metabolism during NASH.Hepatic deletion of Cp effectively remodels BA metabolism by upregulating Cyp7a1 and Cyp8b1,which subsequently leads to enhanced BA synthesis and notable alterations in BA profiles.In conclusion,our studies elucidate the crucial involvement of Cp in NASH,highlighting its significance as a promising therapeutic target for the treatment of this disease.
