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
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
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
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
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.
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.
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 .
