Ceruloplasmin, a reliable marker of fibrosis in chronic hepatitis B virus patients with normal or minimally raised alanine aminotransferase

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.

Ceruloplasmin-ferroportin system of iron traffic in vertebrates

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.

Serum ceruloplasmin can predict liver fibrosis in hepatitis B virusinfected patients

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.

An inhibition of ceruloplasmin expression induced by cerebral ischemia in the cortex and hippocampus of rats

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.

Ceruloplasmin or Fibronectin Synergism with Quartz Dust on Stimulating Collagen Gene Transcription in Human 2BS Fibroblast

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

Evaluation of Glutathione-S-transferase and ceruloplasmin levels in gingival crevicular fluid and gingival tissue as diagnostic markers for chronic periodontitis

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 .

Correlation of Ceruloplasmin with Biomarkers of Cardiac Remodelling and Myofibrosis in Patients with Acute Decompensated Heart Failure Referred to a Tertiary Nurse Lead Heart Failure Clinic

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.

INTRACELLULAR CERULOPLASMIN (CP) IN NORMAL AND LEUKEMIC BLOOD LEUCOCYTES

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).

STUDY ON SERUM CERULOPLASMIN LEVELS IN VARIOUS CONDITIONS AND TYPES OF LEUKEMIA

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).

Ceruloplasmin levels in human sera from various diseases and their correlation with patient’s age and gender

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.

The Role of Serum Ceruloplasmin and Oxidative Stress Markers in Primary Open Angle Glaucoma

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.

Association of bilirubin and protein thiols in relation to copper and ceruloplasmin in hyperbilirubinemic patients

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.

Targeting hepatic ceruloplasmin mitigates nonalcoholic steatohepatitis by modulating bile acid metabolism

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.

星形胶质细胞敲除铜蓝蛋白对小鼠脑铁代谢的影响

目的探讨铜蓝蛋白(CP)在脑铁代谢中的作用机制。方法将CP^(flox/flox)小鼠与^(GFAP)-cre小鼠杂交,得到胶质纤维酸性蛋白(^(GFAP))-cre介导的CP基因敲除小鼠,即CP^(GFAP)cKO小鼠。6月龄88只雄性小鼠被分为WT、^(GFAP)-cre、CP^(flox/flox)和CP^(GFAP)cKO 4组。通过基因型鉴定、免疫荧光染色和Western blotting方法检测星形胶质细胞是否特异性敲除CP;Morris水迷宫实验检测星形胶质细胞敲除CP的小鼠学习和记忆功能;通过电感耦合等离子体质谱法(ICP-MS)和同步辐射微束X线荧光光谱法(μ-XRF)检测皮层、海马区铁水平;血清和组织铁试剂盒测定血清和肝铁含量。结果基因型鉴定、免疫荧光染色和Western blotting结果确认星形胶质细胞特异性敲除CP基因小鼠建立模型成功;Moris水迷宫实验结果观察到星形胶质细胞特异性敲除CP基因,小鼠的学习记忆能力明显降低;ICP-MS、μ-XRF结果显示,皮层区和海马区铁含量显著下降;而血清铁和肝铁含量没有明显变化。结论星形胶质细胞特异性敲除CP基因的小鼠的学习记忆能力下降与脑铁降低密切相关;CP的主要功能可能是协助脑细胞摄取铁。

血流感染患者外周血铁死亡相关指标与病情严重程度的相关性

目的 分析血流感染患者外周血铁代谢指标和铁死亡基因表达与疾病严重程度的相关性。方法 选取2022年8月至2023年5月安徽医科大学第二附属医院98例血流感染患者为研究对象,根据是否发生脓毒症分为非脓毒症组(n=51)和脓毒症组(n=47),另外选取体检健康人20名为对照组;脓毒症患者根据病情严重程度分为一般脓毒症组(n=18)和脓毒性休克组(n=29)。比较各组入院48 h内外周血血清铁代谢指标、铁调素及铜蓝蛋白水平;实时荧光定量逆转录PCR(RT-qPCR)法检测铁死亡相关基因[谷胱甘肽过氧化物酶4(GPX4)、血红素加氧酶-1(HO-1)、热休克蛋白B1(HSPB1)]的表达水平。结果 共纳入98例血培养阳性的单种细菌性血流感染患者,分离出病原菌共计98株,其中革兰阴性菌63株(64.29%),革兰阳性菌30株(30.61%),真菌5株(5.10%);血流感染脓毒症组患者以革兰阴性菌感染为主,与非脓毒症组比较差异有统计学意义(P<0.05)。三组铁代谢指标血清铁、铁蛋白、转铁蛋白、总铁结合力以及铁调素和铜蓝蛋白水平整体差异有统计学意义(P<0.05),铁死亡基因GPX4、HO-1和HSPB1的mRNA表达在总体上差异有统计学意义(P<0.05)。血流感染脓毒症组患者血清中铁代谢相关蛋白如铁蛋白、铁调素和铜蓝蛋白以及铁死亡相关基因HO-1和HSPB1的mRNA水平均显著高于非脓毒症组及对照组(P<0.05),而GPX4 mRNA水平则显著低于非脓毒症组及对照组(P<0.05)。同样地,脓毒性休克组患者血清中铁蛋白、铁调素、铜蓝蛋白以及HSPB1和HO-1的mRNA表达水平均显著高于一般脓毒症组(P<0.05),而GPX4 mRNA表达水平则显著低于一般脓毒症组(P<0.05)。相关性分析结果显示,血清中铁蛋白、铁调素、铜蓝蛋白水平与脓毒症严重程度呈显著正相关(P<0.05)。结论 铁代谢相关蛋白铁调素、转铁蛋白和铜蓝蛋白以及铁死亡相关基因GPX4、HO-1和HSPB1的mRNA表达水平与血流感染脓毒症的发生发展密切相关,其机制还需深入研究。

铜代谢异常在帕金森发病机制中的研究进展

帕金森病是一种与大脑铜代谢异常有关的神经退行性疾病,铜代谢异常导致α-突触核蛋白-铜络合物的错误折叠和聚集是帕金森病的重要病理标志。铜代谢是指有铜离子参与的细胞代谢过程,与帕金森病中α-突触核蛋白聚集、多巴胺代谢、线粒体功能障碍、氧化应激、铁死亡等发病机制密切相关。在本综述中,我们通过研究铜代谢异常在帕金森病中发挥病理作用的机制,描述铜发挥其毒性的分子代谢机制,以期为进一步完善作用机制和药物的开发提供依据和帮助。

母体尿液铜蓝蛋白、子宫动脉搏动指数与妊娠前BMI联合用于子痫前期早期预测的价值研究

目的探讨候选蛋白联合子宫动脉多普勒超声和临床危险因素对子痫前期(PE)的预测价值。方法选取2021年1月1日至12月31日在无锡市妇幼保健院接受产前检查并分娩的60例PE孕妇作为研究对象,分为12例发现集和48例验证集。另外纳入同期同一医院60例无妊娠期并发症的正常孕妇作为对照。于孕11~13^(+6)周留存所有孕妇的尿液上清,使用超高效液相色谱-质谱法(UPLC-MS)和酶联免疫吸附试验法检测尿液上清蛋白;同时采用四维彩色多普勒超声记录子宫动脉搏动指数(UtA-PI);采用免疫组织化学染色法分析胎盘组织中蛋白表达。结果经UPLC-MS分析,在发现集中证实铜蓝蛋白在PE组上调,被作为候选蛋白进行验证。在验证集中,PE组孕妇在妊娠早期平均UtA-PI和尿液铜蓝蛋白均显著高于正常孕妇组(P<0.05)。尿液上清铜蓝白、妊娠前体重指数和异常UtA-PI可很好地预测在妊娠20周后出现PE的女性,灵敏度和特异度分别为0.813和0.937。此外,尿液上清铜蓝蛋白水平与胎盘组织铜蓝蛋白免疫组化平均光密度值呈正相关(r=0.624,P<0.001)。结论尿液铜蓝蛋白可能是PE的一种新的生物标志物,联合子宫动脉搏动指数和临床危险因素可能有助于PE的早期预测。

铜蓝蛋白在脂质代谢稳态调控中作用的研究进展

血浆铜蓝蛋白(ceruloplasmin,Cp)是肝脏分泌的重要蛋白质,在人体的铜离子分布和运输中扮演关键角色,并在维持铜离子稳态方面起重要作用。此外,Cp还是一种亚铁氧化酶,参与人体内铁离子的代谢。研究表明,Cp与糖尿病和心血管疾病等代谢相关疾病有密切关系。近来研究发现,Cp也参与脂质代谢的调控过程。脂质代谢平衡涉及体内脂质合成、脂肪水解、脂肪酸氧化、脂质运输和吸收等过程。脂质代谢紊乱会导致人体代谢紊乱和心血管并发症的发生。Cp通过多种方式调控脂质代谢。一方面,它通过亚铁氧化酶活性参与调节氧化应激,即在铁代谢和氧化还原反应中发挥作用。另一方面,它通过铜及含铜的代谢酶参与胆固醇、脂蛋白和脂肪酸等物质代谢过程的调控。因此,Cp通过影响铜或铁依赖性酶和相关通路在铜和铁的稳态中发挥作用进而调控脂质代谢。尽管已经发现Cp与脂质代谢密切关联的现象,但仍需要进一步研究Cp进行脂质代谢调控的确切机制。该综述总结了Cp在脂质代谢中的作用及其研究进展,以期为脂质代谢紊乱相关疾病的研究和治疗提供新的思路。

CP、Cys-C、RBP及其联合检测在喀什地区维吾尔族慢性肾脏疾病中的诊断价值

目的分析尿外泌体铜蓝蛋白(CP)、血清胱抑素C(Cys-C)、视黄醇结合蛋白(RBP)及其联合检测对喀什地区维吾尔族早期慢性肾脏疾病(CKD)的诊断价值。方法选取2019年1月—2023年1月在新疆喀什地区第一人民医院就诊的225例维吾尔族CKD患者纳入CKD组,另选取同期在体检中心接受健康检查的186例维吾尔族体检者纳入健康对照组。收集两组的尿外泌体CP、血清Cys-C及RBP值。采用logistic回归分析影响早期CKD的因素,绘制受试者工作特征(ROC)曲线分析CP、Cys-C、RBP及其联合检测对早期CKD的临床诊断效能。结果与健康对照组比较,CKD组患者的血清白蛋白、C反应蛋白、血尿素、血沉均明显升高(P<0.05),肾小球滤过率降低(P<0.05)。与健康对照组比较,CKD组尿外泌体CP、血清Cys-C及RBP表达均明显升高(P<0.001)。Logistic回归分析显示,尿外泌体CP、血清Cys-C及RBP是影响早期CKD的独立因素(P<0.001)。ROC曲线分析显示,与尿外泌体CP、血清Cys-C、血清RBP比较,联合检测(并联)诊断早期CKD的AUC、特异度均明显升高。结论早期CKD患者的尿外泌体CP、血清Cys-C、血清RBP均明显升高,尿外泌体CP、血清Cys-C、血清RBP均可用于诊断早期CKD,但联合检测(并联)的诊断效能更高,为尽早诊断CKD提供参考。

Menkes病的临床特点(附1例报告)

目的 探讨ATP7A基因变异引起的Menkes病(MD)的临床特点。方法 回顾性分析1例MD患儿的临床资料,并进行文献复习。结果 本例患儿为7月龄男婴,首发症状为癫痫、喂养困难和精神运动发育迟滞,体征有特殊面容、头发异常、漏斗胸及低张力。生化检查发现血清铜蓝蛋白、血清铜减低。头颅MRI呈弥漫性脑萎缩、脑发育不良、硬膜下积液。基因检测显示X染色体上ATP7A基因剪接位点存在新发半合子变异c.2916+2(IVS14)T>C,验证其母为表型正常的杂合携带者。结论 MD多于婴幼儿时期起病,可导致神经系统、结缔组织等多系统受累,需结合基因检测进行诊断。