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甲状腺机能障碍病人血清弹力纤维酶抑制活性
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作者 J.Wortsman 高嘉明 《地方病译丛》 北大核心 1993年第1期26-28,共3页
弹性蛋白是存在于结缔组织中的一种纤维蛋白,具有特殊的弹性,牵拉放松后能立即完全复原。弹性蛋白和有关的微纤维结构一起构成主要存在于肺和皮肤的弹性纤维。弹性纤维由弹性蛋白酶——一组主要由中性白细胞释放的多种蛋白水解酶——降... 弹性蛋白是存在于结缔组织中的一种纤维蛋白,具有特殊的弹性,牵拉放松后能立即完全复原。弹性蛋白和有关的微纤维结构一起构成主要存在于肺和皮肤的弹性纤维。弹性纤维由弹性蛋白酶——一组主要由中性白细胞释放的多种蛋白水解酶——降解。弹性蛋白酶活性往往受数种血清因子抑制,其中最主要的是肝糖蛋白 A—1—AT。 展开更多
关键词 甲状腺疾病 弹力蛋白 肝糖蛋白
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Full-length core sequence dependent complex-type glycosylation of hepatitis C virus E2 glycoprotein 被引量:10
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作者 CarolineStaib GerdSutter 《World Journal of Gastroenterology》 SCIE CAS CSCD 2002年第3期499-504,共6页
AIM: To study HCV polyprotein processing is important for the understanding of the natural history of HCV and the design of vaccines against HCV. The purpose of this study is to investigate the affection of context se... AIM: To study HCV polyprotein processing is important for the understanding of the natural history of HCV and the design of vaccines against HCV. The purpose of this study is to investigate the affection of context sequences on hepatitis C virus (HCV) E2 processing. METHODS: HCV genes of different lengths were expressed and compared in vaccinia virus/T7 system with homologous patient serum S94 and mouse anti-serum M( E2116) raised against E.coli -derived E2 peptide, respectively.Deglycosylation analysis and GNA ( Galanthus nivalus ) lectin binding assay were performed to study the post-translational processing of the expressed products. RESULTS: E2 glycoproteins with different molecular weights (-75 kDa and -60 kDa) were detected using S94 and M( E2116), respectively. Deglycosylation analysis showed that this difference was mainly due to different glycosylation. Endo H resistance and its failure to bind to GNA lectin demonstrated that the higher molecular weight form (75 kDa) of E2 was complex-type glycosylated, which was readily recognized by homologous patient serum S94. Expression of complex-type glycosylated E2 could not be detected in all of the core-truncated constructs tested, but readily detected in constructs encoding full-length core sequences. CONCLUSION: The upstream conserved full-length core coding sequence was required for the production of E2 glycoproteins carrying complex-type N-glycans which reacted strongly with homologous patient serum and therefore possibly represented more mature forms of E2. As complex-type N-glycans indicated modification by Golgi enzymes, the results suggest that the presence of full-length core might be critical for E1/E2 complex to leave ER. Our data may contribute to a better understanding of the processing of HCV structural proteins as well as HCV morphogenesis. 展开更多
关键词 Animals Cell Line GLYCOSYLATION Hela Cells HEPACIVIRUS Hepatitis C Antibodies Humans Molecular Weight Protein Processing Post-Translational Research Support Non-U.S. Gov't Viral Envelope Proteins
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Down-regulation of extracellular signal-regulated kinase 1/2 activity in P-glycoprotein-mediated multidrug resistant hepatocellular carcinoma cells 被引量:14
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作者 Feng Yan Xiao-Min Wang +1 位作者 Chao Pan Quan-Ming Ma 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第12期1443-1451,共9页
AIM: To study the expression and phosphorylation of extracellular signal-regulated kinase (ERK) i and ERK2 in multidrug resistant (MDR) hepatocellular carcinoma (HCC) cells.METHODS: MDR HCC cell lines, HepG2/a... AIM: To study the expression and phosphorylation of extracellular signal-regulated kinase (ERK) i and ERK2 in multidrug resistant (MDR) hepatocellular carcinoma (HCC) cells.METHODS: MDR HCC cell lines, HepG2/adriamycin (ADM) and SMMC7721/ADM, were developed by exposing parental cells to stepwise increasing concentrations of ADM. MTT assay was used to determine drug sensitivity. Flow cytometry was employed to analyze cell cycle distribution and measure cell P-glycoprotein (P-gp) and multidrug resistant protein 1 (MRP1) expression levels. ERK1 and ERK2 mRNA expression lev-ls were measured by quantitative real-time PCR (QRTPCR). Expression and phosphorylation of ERK1 and ERK2 were analyzed by Western blot.RESULTS: MTT assay showed that HepG2/ADM andSMMC7721/ADM were resistant not only to ADM, but also to multiple anticancer drugs. The P-gp expression was over 10-fold higher in HepG2/ADM cells than in HepG2 cells (8.92% ±0.22% vs 0.88% ± 0.05%, P 〈 0.001) and over 4-fold higher in SMMC7721/ADM cells than in SMMC7721 cells (7.37% ± 0.26% vs 1.74% ± 0.25%, P 〈 0.001). However, the MRP1 expression was not significantly higher in HepG2/ADM and SMMC7721/ADM cells than in parental cells. In addition, the percentage of MDR HepG2/ADM and SMMC7721/ADM cells was significantly decreased in the G0/G1 phase and increased in the the S phase or G2/M phase. QRT-PCR analysis demonstrated that the ERK1 and ERK2 mRNA expression increased apparently in HepG2/ADM cells and decreased significantly in SMMC7721/ADM cells. Compared with the expression of parental cells, ERK1 and ERK2 protein expressions were markedly decreased in SMMC7721/ADM cells. However, ERK2 protein expression was markedly increased while ERK1 protein expression had no significant change in HepG2/ADM cells. Phosphorylation of ERK1 and ERK2 was markedly decreased in both HepG2/ADM and SMMC7721/ADM MDR cells.CONCLUSION: ERK1 and ERK2 activities are downregulated in P-gp-mediated MDR HCC cells. ERK1 or ERK2 might be a potential drug target for circumventing MDR HCC cells, 展开更多
关键词 Multidrug resistance Extracellular signalregulated MAP kinases Hepatocellular carcinoma P-GLYCOPROTEIN Multidrug resistance-associated protein
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Construction of a fusion protein expression vector MK-EGFP and its subcellular localization in different carcinoma cell lines 被引量:6
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作者 Li-Cheng Dai Di-Yong Xu +5 位作者 Xing Yao Li-Shan Min Ning Zhao Bo-Ying Xu Zheng-Ping Xu Yong-Liang Lu 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第47期7649-7653,共5页
AIM: To construct an expression plasmid encoding human wild-type midkine (MK) and enhanced green fluorescence protein (EGFP) fusion protein (MK-EGFP), and to analyze the subcellular localization of MK in differ... AIM: To construct an expression plasmid encoding human wild-type midkine (MK) and enhanced green fluorescence protein (EGFP) fusion protein (MK-EGFP), and to analyze the subcellular localization of MK in different cardnoma cell lines. METHODS: Two kinds of MK coding sequences with or without signal peptide were cloned into plasmid pEGFP-N2, and the recombinant plasmids constructed were introduced into HepG2, MCF7 and DU145 cells, respectively, by transfection. With the help of laser scanning confocal microscopy, the expression and subcellular localization of MK-GFP fusion protein could be detected. RESULTS: Compared with the GFP control, in which fluorescence was detected diffusely over the entire cell body except in the nucleolus, both kinds of fusion protein MK-GFP were localized exclusively to the nucleus and accumulated in the nucleolus in the three kinds of cancer cell lines. CONCLUSION: This study reveals the specific nucleolar translocation independent of signal peptide, which may be involved in the mechanism that MK works. It provides valuable evidence for further study on the functions of MK in nucleus and its possible mechanisms, in which ribosomal RNA transcription and ribosome assembly are involved. 展开更多
关键词 MIDKINE Subcellular localization Laser scanning confocal microscopy
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Relationship between therapeutic efficacy of arterial infusion chemotherapy and expression of P-glycoprotein and p53 protein in advanced hepatocellular carcinoma 被引量:7
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作者 MasahideAkimoto MasaharuYoshikawa +4 位作者 MasaakiEbara TsunenobuSato HiroyukiFukuda HiromitsuSaisho Fukuo Kondo 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第6期868-873,共6页
AIM: To investigate the relationship between the chemotherapeutic drug efficacy and the expression of P-glycoprotein (PGP) and p53 protein in advanced hepatocellular carcinoma (HCC). METHODS: The study was condu... AIM: To investigate the relationship between the chemotherapeutic drug efficacy and the expression of P-glycoprotein (PGP) and p53 protein in advanced hepatocellular carcinoma (HCC). METHODS: The study was conducted on 41 patients with advanced HCC who were treated by repeated arterial infusion chemotherapy. Biopsy specimens from the tumor were collected before the start of treatment in all the patients, and the specimens were stored frozen until immunohistochemical staining, which was performed after the start of treatment, to detect PGP and p53 protein expressions. Twenty of the fortyone patients were treated with an anthracycline drug (epirubicin hydrochloride; anthracycline group), and the remaining 21 were treated with a non-anthracycline drug (mitoxantrone hydrochloride in 11 patients and carboplatin in 10 patients; non-anthracycline group). The relationship between the chemotherapeutic efficacy and the results of immunostaining were compared between the two groups. RESULTS: Before the start of the treatment, PGPpositive rate was 90.2% (strongly-positive, 36.6%) and p53 protein-positive rate was 34.1% (strongly-positive, 19.5%). In the anthracycline group, the response rate was 40.0%. The number of patients showing poor response to the treatment was significantly larger in the patients with strongly positive PGP expression (P= 0.005), and their prognoses were poor (P= 0.001). in the nonanthracycline group, the response rate was 42.9%,and there was no significant relationship between the chemotherapeutic drug efficacy and the PGP or p53 protein expression. When only the data from the 11 patients treated with anthraquinone drug, mitoxantrone, were analyzed, however, the number of patients who showed poor response to treatment was significantly higher among the p53-positive patients (P= 0.012), irrespective of the survival outcome. CONCLUSION: The chemotherapeutic efficacy with an anthracycline drug for advanced HCC can be predicted by immunohistochemical analysis of PGP expression. Similarly, immunostaining to evaluate p53 protein may be useful to predict the response in patients treated with an anthraquinone drug. 展开更多
关键词 Arterial infusion chemotherapy Hepatocellularcarcinoma P-GLYCOPROTEIN p53 protein
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Fatty Acid Synthase and Hormone-sensitive Lipase Expression in Liver Are Involved in Zinc-α2-glycoprotein-induced Body Fat Loss in Obese Mice 被引量:12
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作者 Feng-ying Gong Jie-ying Deng Hui-juan Zhu Hui Pan Lin-jie Wang Hong-bo Yang 《Chinese Medical Sciences Journal》 CAS CSCD 2010年第3期169-175,共7页
Objective To explore the effects of zinc-0t2-glycoprotein (ZAG) on body weight and body fat in high-fat-diet (HF1))-induced obesity in mice and the possible mechanism. Methods Thirty-six male mice were fed with ... Objective To explore the effects of zinc-0t2-glycoprotein (ZAG) on body weight and body fat in high-fat-diet (HF1))-induced obesity in mice and the possible mechanism. Methods Thirty-six male mice were fed with standard food (SF) (n=9) and HFD (n=27), respectively. Five weeks later, 9 mice fed with HFD were subjected to ZAG expression plasmid DNA transfection by liposome transfection method, and another 9 mice to negative control plasmid transfection. Two weeks later, serum ZAG level in the mice was assayed by Western blot, and the effects of ZAG over-expression on body weight, body fat, serum biochemical indexes, and adipose tissue of obese mice were evaluated. The mRNA expressions of fatty acid synthase (FAS) and hormone sensitive lipase (HSL) in liver tissue were deterlnined by reverse transcription-polymerase chain reaction. Results Serum ZAG level significantly lowered in simple HFD-fed mice in comparison to SF-fed mice (0.51±0.10 AU vs. 0.75±0.07 AU, P〈0.01). Further statistical analysis demonstrated that ZAG level was negatively correlated with body weight (r =-0.56, P〈0.001), epididymal fat mass (r=-0.67, P〈O. 001), percentage of epididymal fat (r= 0.65, P〈0.001), and increased weight (r= 0.57, P〈0.001) in simple SF- and HFD fed mice. ZAG over-expression in obese mice reduced body weight and the percentage of epididyreal fat. Furthermore, FAS mRNA expression decreased (P〈0.01) and HSL mRNA expression increased (P〈0.001) in the liver in ZAG over-expressing mice. Conclusions ZAG is closely related to obesity. Serum ZAG level is inversely correlated with body weight and percentage of body fat. The action of ZAG is associated with reduced FAS expression and increased HSL expression in the liver of obese mice. 展开更多
关键词 zinc-α2-glycoprotein adipose tissue fatty acid synthase hormone-sensitivelipase OBESITY
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Quantitative proteomic analysis for high-throughput screening of differential glycoproteins in hepatocellular carcinoma serum 被引量:3
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作者 Hua-Jun Gao Ya-Jing Chen +5 位作者 Duo Zuo Ming-Ming Xiao Ying Li Hua Guo Ning Zhang Rui-Bing Chen 《Cancer Biology & Medicine》 SCIE CAS CSCD 2015年第3期246-254,共9页
Objective: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths. Novel serum biomarkers are required to increase the sensitivity and specificity of serum screening for early HCC diagnosis. Thi... Objective: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths. Novel serum biomarkers are required to increase the sensitivity and specificity of serum screening for early HCC diagnosis. This study employed a quantitative proteomic strategy to analyze the differential expression of serum glycoproteins between HCC and normal control serum samples. Methods: Lectin affinity chromatography (LAC) was used to enrich glycoproteins from the serum samples. Quantitative mass spectrometric analysis combined with stable isotope dimethyl labeling and 2D liquid chromatography (LC) separations were performed to examine the differential levels of the detected proteins between HCC and control serum samples. Western blot was used to analyze the differential expression levels of the three serum proteins. Results: A total of 2,280 protein groups were identified in the serum samples from HCC patients by using the 2D LC-MS/MS method. Up to 36 proteins were up-regulated in the HCC serum, whereas 19 proteins were down-regulated. Three differential glycoproteins, namely, fibrinogen gamma chain (FGG), FOS-like antigen 2 (FOSL2), and a-l, 6-mannosylglycoprotein 6-^-N-acetylglucosaminyltransferase B (MGATSB) were validated by Western blot. All these three proteins were up-regulated in the HCC serum samples. Conclusion: A quantitative glycoproteomic method was established and proven useful to determine potential novel biomarkers for HCC. 展开更多
关键词 GLYCOPROTEIN hepatocellular carcinoma (HCC) mass spectrometry PROTEOMICS SERUM
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Impact of asialoglycoprotein receptor deficiency on the development of liver injury 被引量:2
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作者 Serene ML Lee Carol A Casey Benita L McVicker 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第10期1194-1200,共7页
The asialoglycoprotein (ASGP) receptor is a wellcharacterized hepatic receptor that is recycled via the common cellular process of receptor-mediated endocytosis (RME). The RME process plays an integral part in the... The asialoglycoprotein (ASGP) receptor is a wellcharacterized hepatic receptor that is recycled via the common cellular process of receptor-mediated endocytosis (RME). The RME process plays an integral part in the proper trafficking and routing of receptors and ligands in the healthy cell. Thus, the missorting or altered transport of proteins during RME is thought to play a role in several diseases associated with hepatocyte and liver dysfunction. Previously, we examined in detail alterations that occur in hepatocellular RME and associated receptor functions as a result of one particular liver injury, alcoholic liver disease (ALD). The studies revealed profound ethanol- mediated impairments to the ASGP receptor and the RME process, indicating the importance of this receptor and the maintenance of proper endocytic events in normal tissue. To further clarify these observations, studies were performed utilizing knockout mice (lacking a functional ASGP receptor) to which were administered several liver toxicants. In addition to alcohol, we examined the effects following administration of anti- Fas (CD95) antibody, carbon tetrachloride (CCh) and lipopolysaccharide (LPS)/galactosamine. The results of these studies demonstrated that the knockout mice sustained enhanced liver injury in response to all of the treatments, as shown by increased indices of liver damage, such as enhancement of serum enzyme levels, histopathological scores, as well as hepatocellular death. Overall, the work completed to date suggests a possible link between hepatic receptors and liver injury. In particular, adequate function and content of the ASGP receptor may provide protection against various toxinmediated liver diseases. 展开更多
关键词 Asialoglycoprotein receptor Asialoglycoproteinreceptor deficient mice Receptor-mediatedendocytosis ALCOHOL Carbon tetrachloride Anti-Fas Lipopolysaccharide/galactosamine Toxicant-induced liverinjury
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INHIBITION OF MELATONIN BIOSYNTHESIS ACTIVATES PROTEIN KINASE A AND INDUCES ALZHEIMER-LIKE TAU HYPERPHOSPHORYLATION IN RATS 被引量:3
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作者 Ling-qiangZhu Shao-huiWang Zhi-qunLing QunWang Mao-qiongHu Jian-zhiWang 《Chinese Medical Sciences Journal》 CAS CSCD 2005年第2期83-87,共5页
Objective To investigate effect of inhibiting melatonin biosynthesis on activities of protein kinase A (PKA), glycogen synthase kinase-3 (GSK-3) and tau phosphorylation at PS214 and M4 epitopes using haloperidol, a sp... Objective To investigate effect of inhibiting melatonin biosynthesis on activities of protein kinase A (PKA), glycogen synthase kinase-3 (GSK-3) and tau phosphorylation at PS214 and M4 epitopes using haloperidol, a specific inhibitor of 5-hydroxyindole-O-methyltransferase. Methods Brain ventricular and intraperitoneal injections were used for haloperidol administration, Western blots for tau phosphorylation, 32P-labeling for PKA and GSK-3 activity, and high performance liquid chromatograph for detection of serum melatonin levels. Results Haloperidol injection through the lateral ventricle and intraperitoneal reinforcement significantly stimulated PKA activity with a concurrent hyperphosphorylation of tau at M4 (Thr231/Ser235) and PS214 (Ser214) sites. Prior treatment of the rats using melatonin supplement for one week and reinforcement during the haloperidol administration arrested PKA activity and attenuated tau hyperphosphorylation. GSK-3 activity showed no obvious change after haloperidol injection, however, melatonin supplements and reinforcements during haloperidol infusion inactivated basal activity of GSK-3. Conclusion Decreased melatonin may be involved in Alzheimer-like tau hyperphosphorylation, and overactivation of PKA may play a crucial role in this process. 展开更多
关键词 Alzheimer's disease HALOPERIDOL MELATONIN TAU protein kinase A
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Hepatic expression and cellular distribution of the glucose transporter family 被引量:5
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作者 Sumera Karim David H Adams Patricia F Lalor 《World Journal of Gastroenterology》 SCIE CAS CSCD 2012年第46期6771-6781,共11页
Glucose and other carbohydrates are transported into cells using members of a family of integral membrane glucose transporter (GLUT) molecules. To date 14 members of this family, also called the solute carrier 2A prot... Glucose and other carbohydrates are transported into cells using members of a family of integral membrane glucose transporter (GLUT) molecules. To date 14 members of this family, also called the solute carrier 2A proteins have been identified which are divided on the basis of transport characteristics and sequence similarities into several families (Classes 1 to 3). The expression of these different receptor subtypes varies between different species, tissues and cellular subtypes and each has differential sensitivities to stimuli such as insulin. The liver is a contributor to metabolic carbohydrate homeostasis and is a major site for synthesis, storage and redistribution of carbohydrates. Situations in which the balance of glucose homeostasis is upset such as diabetes or the metabolic syndrome can lead metabolic disturbances that drive chronic organ damage and failure, confirming the importance of understanding the molecular regulation of hepatic glucose homeostasis. There is a considerable literature describing the expression and function of receptors that regulate glucose uptake and release by hepatocytes, the most import cells in glucose regulation and glycogen storage. However there is less appreciation of the roles of GLUTs expressed by non parenchymal cell types within the liver, all of which require carbohydrate to function. A better understanding of the detailed cellular distribution of GLUTs in human liver tissue may shed light on mechanisms underlying disease pathogenesis. This review summarises the available literature on hepatocellular expression of GLUTs in health and disease and highlights areas where further investigation is required. 展开更多
关键词 Hepatic Liver Glucose transporters Glucose Transport Hepatocyte
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E2 GLYCOPROTEIN OF GENOTYPE Ⅲ CHINESE ISOLATES OF HEPATITIS C VIRUS EXPRESSED IN MAMMALIAN CELL AS ANTIGEN FOR ANTI-E2 ANTIBODY DETECTION
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作者 吴朝栋 陶其敏 《Chinese Medical Sciences Journal》 CAS CSCD 1998年第2期77-79,共3页
Expression vector inserted with E2/NS1 gene derived from genotype Ⅲ Chinese isolates of HCV was transfected into mammalian cells to express E2 glycoprotein. Expressed protein was used as antigen for an- ti-E2 antibod... Expression vector inserted with E2/NS1 gene derived from genotype Ⅲ Chinese isolates of HCV was transfected into mammalian cells to express E2 glycoprotein. Expressed protein was used as antigen for an- ti-E2 antibody detection in 19 cases of hepatitis C patients by Western blot. It was first to express E2 gly- coprotein of genotype Ⅲ Chinese hepatitis C virus isolates. For anti-E2 detection, 14 cases of patients were positive of antibodies against E2(73. 7 % ). These results indicated that E2 glycoprotein expressed in mam-malian cells had good immunogenicity and cross reactivity to serum infected with genotype Ⅱ Chinese hep-atitis C virus isolates. 展开更多
关键词 hepatitis C virus protein expression GENOTYPE
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Increased expression of chondroitin sulphate proteoglycans in rat hepatocellular carcinoma tissues 被引量:2
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作者 Xiao-Li Jia Si-Yuan Li +5 位作者 Shuang-Suo Dang Yan-An Cheng Xin Zhang Wen-Jun Wang Clare E Hughes Bruce Caterson 《World Journal of Gastroenterology》 SCIE CAS CSCD 2012年第30期3962-3976,共15页
AIM:To investigate the expression of chondroitin sulphate proteoglycans(CSPGs)in rat liver tissues of hepatocellular carcinoma(HCC).METHODS:Thirty male Sprague Dawley rats were randomly divided into two groups:control... AIM:To investigate the expression of chondroitin sulphate proteoglycans(CSPGs)in rat liver tissues of hepatocellular carcinoma(HCC).METHODS:Thirty male Sprague Dawley rats were randomly divided into two groups:control group(n=10) and HCC model group(n=20).Rats in the HCC model groups were intragastrically administrated with 0.2%(w/v)N-diethylnitrosamine(DEN)every 5 d for 16 wk,whereas 0.9%(w/v)normal saline was administered to rats in the control group.After 16 wk from the initiation of experiment,all rats were killed and livers were collected and fixed in 4%(w/v)paraformaldehyde.All tissues were embedded in paraffin and sectioned.Histological staining(hematoxylin and eosin and Toluidine blue)was performed to demonstrate the onset of HCC and the content of sulphated glycosaminoglycan(sGAG).Immunohistochemical staining was performed to investigate the expression of chondroitin sulphate(CS)/dermatan sulphate(DS)-GAG,heparan sulphate(HS)-GAG,keratan sulphate(KS)-GAG in liver tissues.Furthermore,expression and distribution of CSPG family members,including aggrecan,versican,biglycan and decorin in liver tissues,were also immunohistochemically determined.RESULTS:After 16 wk administration of DEN,malignant nodules were observed on the surface of livers from the HCC model group,and their hepatic lobule structures appeared largely disrupted under microscope.Toluidine blue staining demonstrated that there was an significant increase in sGAG content in HCC tissues when compared with that in the normal liver tissues from the control group[0.37±0.05 integrated optical density per stained area(IOD/area)and 0.21± 0.01 IOD/area,P<0.05].Immunohistochemical studies demonstrated that this increased sGAG in HCC tissues was induced by an elevated expression of CS/DS(0.28±0.02 IOD/area and 0.18±0.02 IOD/area,P< 0.05)and HS(0.30±0.03 IOD/area and 0.17±0.02 IOD/area,P<0.01)but not KS GAGs in HCC tissues.Further studies thereby were performed to investigate the expression and distribution of several CSPG components in HCC tissues,including aggrecan,versican,biglycan and decorin.Interestingly,there was a distinct distribution pattern for these CSPG components between HCC tissues and the normal tissues.Positive staining of aggrecan,biglycan and decorin was localized in hepatic membrane and/or pericellular matrix in normal liver tissues;however,their expression was mainly observed in the cytoplasm,cell membranes in hepatoma cells and/or pericellular matrix within HCC tissues.Semi-quantitative analysis indicated that there was a higher level of expression of aggrecan(0.43± 0.01 and 0.35±0.03,P<0.05),biglycan(0.32±0.01 and 0.25±0.01,P<0.001)and decorin(0.29±0.01 and 0.26±0.01,P<0.05)in HCC tissues compared with that in the normal liver tissues.Very weak versican positive staining was observed in hepatocytes near central vein in normal liver tissues;however there was an intensive versican distribution in fibrosis septa between the hepatoma nodules.Semi-quantitative analysis indicated that the positive rate of versican in hepatoma tissues from the HCC model group was much higher than that in the control group(33.61%and 21.28%,P <0.05).There was no positive staining in lumican and keratocan,two major KSPGs,in either normal or HCC liver tissues.CONCLUSION:CSPGs play important roles in the onset and progression of HCC,and may provide potential therapeutic targets and clinical biomarkers for this prevalent tumor in humans. 展开更多
关键词 Hepatocellular carcinoma Proteoglycan Chondroitin sulphate Heparan sulphate Keratan sulphate
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Olive oil consumption and non-alcoholic fatty liver disease 被引量:24
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作者 Nimer Assy Faris Nassar +1 位作者 Gattas Nasser Maria Grosovski 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第15期1809-1815,共7页
The clinical implications of non-alcoholic fatty liver diseases(NAFLD)derive from their potential to progress to fibrosis and cirrhosis.Inappropriate dietary fat intake,excessive intake of soft drinks,insulin resistan... The clinical implications of non-alcoholic fatty liver diseases(NAFLD)derive from their potential to progress to fibrosis and cirrhosis.Inappropriate dietary fat intake,excessive intake of soft drinks,insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride(TG)accumulation.An olive oil-rich diet decreases accumulation of TGs in the liver,improves postprandial TGs,glucose and glucagonlike peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver.The principal mechanisms include:decreased nuclear factor-kappaB activation,decreased lowdensity lipoprotein oxidation,and improved insulin resistance by reduced production of inflammatory cytokines(tumor necrosis factor,interleukin-6)and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1.The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids,mainly from olive oil.In this review,we describe the dietary sources of the monounsaturated fatty acids,the composition of olive oil,dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis,clinical and experimental studies that assess the relationship between olive oil and NAFLD,and the mechanism by which olive oil ameliorates fatty liver,and we discuss future perspectives. 展开更多
关键词 Liver steatosis Fatty liver Olive oil Fatty acids Monounsaturated Non-alcoholic steatohepatitis LIPIDS Oleic acid Non-alcoholic fatty liver disease
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Nude mice multi-drug resistance model of orthotopic transplantation of liver neoplasm and Tc-99m MIBI SPECT on p-glycoprotein
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作者 YuHan Xiao-PingChen +1 位作者 Zhi-YongHuang HongZhu 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第22期3335-3338,共4页
AIM: To establish a model of drug-resistant neoplasms using a nude mice model, orthotopic transplantation of liver neoplasm and sporadic abdominal chemotherapy. METHODS: Hepatocellular carcinoma cells HepG2 were cultu... AIM: To establish a model of drug-resistant neoplasms using a nude mice model, orthotopic transplantation of liver neoplasm and sporadic abdominal chemotherapy. METHODS: Hepatocellular carcinoma cells HepG2 were cultured and injected subdermally to form the tumor-supplying mice. The orthotopic drug-resistant tumors were formed by implanting the tumor bits under the envelope of the mice liver and induced by abdominal chemotherapy with Pharmorubicin. Physical examination, ultrasonography, spiral CT and visual inspection were used to examine tumor progression. RT-PCR and immunohistochemistry were used to detect expression of mdr1 mRNA and its encoded protein p-glycoprotein (p-gp). Tc-99m sestamibi scintigraphy was performed by obtaining planar abdominal images at 20 min after injection, and the liver/heart ratios were calculated. RESULTS: Post-implantation mortality was 0% (0/25), tumor implantation success was 90% (22/25), and the rate of implanting successfully for the second time was 100% (3/3). Tumor induction using Pharmorubicin was 80% (16/20). The mdrl mRNA expression of the induced group was 23 times higher than that of the control group, and p-gp protein expression was 13-fold higher compared to the control group. The liver/heart ratio (as assessed in vivo, using Tc-99m radiography) was decreased significantly in the induced group as compared to the control group. CONCLUSION: We have established an in vivo model of mdrl in nude mice by orthotopic transplantation of liver neoplasm coupled to chemotherapy. We propose that identification of drug resistance as characterized by decreased 99mTc-ppm radiography due to enhanced clearance by p-gp may be useful in detecting in vivo drug resistance, as well as a useful tool in designing more effective therapies. 展开更多
关键词 Orthotopic transplantation Liver neoplasm Sporadic abdominal chemotherapy
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Vague relationship between alcohol consumption and metabolic syndrome in nonobese people
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作者 Kei Nakajima Masafumi Saito 《World Journal of Gastroenterology》 SCIE CAS CSCD 2012年第37期5315-5316,共2页
Fatty liver, including non-alcoholic fatty liver disease, is closely associated with metabolic syndrome (MS). Thus, the presence of fatty liver without MS in some conditions may be clinically important. Many studies h... Fatty liver, including non-alcoholic fatty liver disease, is closely associated with metabolic syndrome (MS). Thus, the presence of fatty liver without MS in some conditions may be clinically important. Many studies have shown that compared with no or occasional alcohol intake, moderate alcohol consumption is associated with lower prevalence rates of hypertension and type 2 diabetes, and lower levels of circulating C-reactive protein, a valuable marker for MS and insulin resistance. Considering these findings, light to moderate alcohol consumption has theoretical benefits on fatty liver and MS. Fatty liver, including non-alcoholic fatty liver disease, may be more clinically important than MS, particularly in non-obese individuals, because fatty liver can develop before MS in several conditions, such as regular alcohol consumers. Furthermore, most of the currently used MS criteria are unable to detect "true MS" because of variations in multiple factors such as age, height, medications, and complications. 展开更多
关键词 Alcohol consumption Non-alcoholic fatty liver disease Metabolic syndrome Adult treatment panel
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LOW MOLECULAR WEIGHT HEPARIN DECREASES THE ALBUMINURIA AND RENAL PATHOLOGICAL CHANGES IN DIABETIC NEPHROPATHY RATS
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作者 王锋 邢涛 +1 位作者 汪年松 晏春根 《Medical Bulletin of Shanghai Jiaotong University》 CAS 2010年第2期66-70,共5页
Objective To investigate the renoprotection effect of low molecular weight heparin(LMWH)in diabetic rats.Methods Diabetic rats were induced by injection of steptozotocin(STZ).Rats were randomly divided into three grou... Objective To investigate the renoprotection effect of low molecular weight heparin(LMWH)in diabetic rats.Methods Diabetic rats were induced by injection of steptozotocin(STZ).Rats were randomly divided into three groups:control group,diabetic model group,and LMWH treatment group.The levels of total cholesterol(TC),triglyceride(TG),prothrombin time(PT),kaolin partial thromboplastin time(KPTT),24-hour urinary albumin excretion rate(UAER),and serum soluble P-selectin were determined after 8 weeks.Glomerular morphology was observed by light microscopy.Results The levels of TG,UAER,and P-selectin in LWMH treatment group were lower than those in model group(all P<0.01).The levels of PT and KPTT in LWMH treatment group were shorter than those in model group.And LWMH improved the histological changes of diabetic rats.Conclusion LMWH has some renal protective effects in diabetic rats,partly through down-regulating the expression of P-selectin. 展开更多
关键词 diabetic nephropathy heparin P-selectin
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PSG9 promotes angiogenesis by stimulating VEGFA production and is associated with poor prognosis in hepatocellular carcinoma 被引量:3
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作者 Weiqi Rong Lei Yang +3 位作者 Liyuan Yin Yanning Gao Ting Xiao Shujun Cheng 《Science China(Life Sciences)》 SCIE CAS CSCD 2017年第5期528-535,共8页
Hepatocellular carcinoma(HCC) is a common malignant solid tumor characterized by rich vascularization. Pregnancy-specific glycoprotein 9(PSG9) is a member of the carcinoembryonic antigen(CEA)/PSG family and is produce... Hepatocellular carcinoma(HCC) is a common malignant solid tumor characterized by rich vascularization. Pregnancy-specific glycoprotein 9(PSG9) is a member of the carcinoembryonic antigen(CEA)/PSG family and is produced at high levels during pregnancy. We previously identified PSG9 as an HCC-related protein. However, the expression of PSG9 and its regulation during HCC carcinogenesis remain poorly explored. In the present study, we first found that the levels of PSG9 protein were significantly increased in the plasma of HCC patients. PSG9 overexpression also increased the proliferation ability of an HCC cell line. High expression of PSG9 was associated with angiogenesis by accelerating VEGFA expression. In addition, Cox's proportional hazards model analysis revealed that the plasma level of PSG9 was an independent prognostic factor for overall survival. We propose that PSG9 is a novel indicator of prognosis in patients with HCC and could serve as a novel therapeutic target for HCC. Furthermore,our results indicate that PSG9 protein may facilitate the development of HCC by fostering angiogenesis via promoting VEGFA production in cancer cells. 展开更多
关键词 hepatocellular carcinoma (HCC) PSG9 VEGFA ANGIOGENESIS
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Clinical application of specific antibody against glypican-3 for hepatocellular carcinoma diagnosis 被引量:18
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作者 YU JuanPing MA Qiang +5 位作者 ZHANG Bin MA RuiJuan XU XiGuang LI MingSong XU WeiWen LI Ming 《Science China(Life Sciences)》 SCIE CAS 2013年第3期234-239,共6页
Glypican-3(GPC3) is a promising tumor marker for hepatocellular carcinoma(HCC) diagnosis with high sensitivity and specificity.The aim of this study was to establish an immunohistochemical detection method for GPC3 us... Glypican-3(GPC3) is a promising tumor marker for hepatocellular carcinoma(HCC) diagnosis with high sensitivity and specificity.The aim of this study was to establish an immunohistochemical detection method for GPC3 using the 7D11 monoclonal antibody(7D11 mAb) and evaluate its application for HCC diagnosis.The feasibility of the 7D11 mAb was evaluated by immunohistochemistry performed on adjacent normal liver and intrahepatic cholangiocarcinoma(ICC) samples,Furthermore,the serum GPC3 levels were evaluated in 40 HCC patients,7 ICC patients and 50 healthy donors.The results showed that GPC3 was expressed in 85% of HCC tissues(34/40),but was undetectable in ICC tissues and adjacent normal tissues.GPC3 was significantly increased in the serum of HCC patients(17/40,42.5%) but was undetectable in the serum of ICC patients(0/7,0%) and healthy donors(0/50,0%).This prospective study evaluated the clinical usefulness of 7D11 mAb for GPC3 detection in HCC patients.In conclusion,the use of 7D11 mAb might be good for GPC3 large-scale applications for clinical diagnosis of HCC. 展开更多
关键词 GLYPICAN-3 7Dll monoclonal antibody hepatocellular carcinoma IMMUNOHISTOCHEMISTRY
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α-2-HS-glycoprotein is a potential marker predicting hepatitis B e antigen seroconversion in patients with chronic hepatitis B during treatment with pegylated interferon alfa-2b 被引量:6
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作者 MA Hui WANG JiangHua GUO Fang WEI Lai 《Science China(Life Sciences)》 SCIE CAS 2011年第1期39-47,共9页
The efficacy of interferon (IFN) is limited in about 1/3 of patients with chronic hepatitis B (CHB). We used two-dimensional electrophoresis (2-DE)-based proteomic strategies to identify potential serum markers predic... The efficacy of interferon (IFN) is limited in about 1/3 of patients with chronic hepatitis B (CHB). We used two-dimensional electrophoresis (2-DE)-based proteomic strategies to identify potential serum markers predicting hepatitis B e antigen (HBeAg) seroconversion in these patients during IFN therapy. Two groups of patients were enrolled: training and validation. In the training group, 2-DE experiments and subsequent identification of altered levels of proteins showed that α-2-HS-glycoprotein, leucine-rich α-2-glycoprotein, and haptoglobin were significantly upregulated as compared with baseline levels in the HBeAg seroconversion group, whereas apolipoprotein C-III precursor, leucine-rich α-2-glycoprotein, and α-albumin were downregulated in the non-seroconversion group. For patients with HBeAg seroconversion in the training group, Western blot analyses showed that α-2-HS-glycoprotein levels in 75% of patients were significantly upregulated at the end of the treatment as compared with baseline levels. Subsequent experiments in the validation group showed that α-2-HS-glycoprotein levels were significantly increased at week 4 in 83.33% of patients in the HBeAg seroconversion group. Dynamic changes in the serum level of α-2-HS-glycoprotein may be a potential early marker for predicting HBeAg seroconversion during IFN treatment for CHB. 展开更多
关键词 α-2-HS-glycoprotein pegylated interferon alfa-2b chronic hepatitis B
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