1.Role of HBx in hepatocellular carcinoma development.
Journal of Zhejiang University. Medical sciences 2010;39(3):333-338
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China, which is mainly caused by hepatitis B virus (HBV) infection. The X gene product (HBx) of HBV has extensive trans-activating functions. HBx affects the signal transduction, apoptotic cell death and cell cycle through interaction with variety intracellular proteins in infected hepatocytes. In view of the importance of HBx in HBV replication and in hepatic cell functions, the role of HBx in HCC development has been attracting great attention.
Carcinoma, Hepatocellular
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pathology
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Hepatitis B virus
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genetics
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physiology
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Humans
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Liver Neoplasms
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pathology
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Trans-Activators
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genetics
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physiology
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Virus Replication
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physiology
2.Interleukin-10 Contributes to Therapeutic Effect of Mesenchymal Stem Cells for Acute Liver Failure via Signal Transducer and Activator of Transcription 3 Signaling Pathway.
Hu-Cheng MA ; Xin WANG ; Min-Na WU ; Xin ZHAO ; Xian-Wen YUAN ; Xiao-Lei SHI
Chinese Medical Journal 2016;129(8):967-975
BACKGROUNDMesenchymal stem cells (MSCs) transplantation has been proven to have therapeutic potential for acute liver failure (ALF). However, the mechanism remains controversial. Recently, modulation of inflammation by MSCs has been regarded as a crucial mechanism. The aim of the present study was to explore the soluble cytokines secreted by MSCs and their therapeutic effects in ALF.
METHODSMSCs isolated from Sprague-Dawley rats were identified by fluorescence-activated cell sorting analysis. Conditioned medium derived from MSCs (MSCs-CM) was collected and analyzed by a cytokine microarray. MSCs and MSCs-CM were transplanted into rats with D-galactosamine-induced ALF. Liver function, survival rate, histology, and inflammatory factors were determined. Exogenous recombinant rat interleukin (IL)-10, anti-rat IL-10 antibody, and AG490 (signal transducer and activator of transcription 3 [STAT3] signaling pathway inhibitor) were administered to explore the therapeutic mechanism of MSCs-CM. Statistical analysis was performed with SPSS version 19.0, and all data were analyzed by the independent-sample t-test.
RESULTSThere are statistical differences of the survival curve between ALF+MSCs group and ALF+Dulbecco's modified Eagle's medium (DMEM) group, as well as ALF+MSCs-CM group and ALF+DMEM group (all P < 0.05). Serum alanine aminotransferase (ALT) level in the ALF+MSCs and ALF+MSCs-CM groups was lower than that in the ALF+DMEM group (865.53±52.80 vs. 1709.75±372.12 U/L and 964.72±414.59 vs. 1709.75±372.12 U/L, respectively, all P < 0.05); meanwhile, serum aspartate aminotransferase (AST) level in the ALF+MSCs and ALF+MSCs-CM groups was lower than that in the ALF+DMEM group (2440.83±511.94 vs. 4234.35±807.30 U/L and 2739.83±587.33 vs. 4234.35±807.30 U/L, respectively, all P < 0.05). Furthermore, MSCs or MSCs-CM treatment significantly reduced serum interferon-γ (IFN-γ), IL-1β, IL-6 levels and increased serum IL-10 level compared with DMEM (all P < 0.05). Proteome profile analysis of MSCs-CM indicated the presence of anti-inflammatory factors and IL-10 was the most distinct. Blocking of IL-10 confirmed the therapeutic significance of this cytokine. Phosphorylated STAT3 was upregulated after IL-10 infusion and inhibition of STAT3 by AG490 reversed the therapeutic effect of IL-10.
CONCLUSIONSThe factors released by MSCs, especially IL-10, have the potential for therapeutic recovery of ALF, and the STAT3 signaling pathway may mediate the anti-inflammatory effect of IL-10.
Animals ; Interleukin-10 ; physiology ; Liver ; pathology ; Liver Failure, Acute ; pathology ; therapy ; Male ; Mesenchymal Stem Cell Transplantation ; Rats ; Rats, Sprague-Dawley ; STAT3 Transcription Factor ; physiology ; Signal Transduction ; physiology
4.Comparison of the yearly cycle cosine curve imitative parameters of the clinical features of liver cancer at different longitude and latitude.
Wan-xian YU ; Min-jing ZUO ; Zheng-rong WANG ; He-lang HUANG ; Meng-li XIE ; Bao-chu ZHANG
Chinese Journal of Hepatology 2003;11(6):347-349
OBJECTIVETo explore whether there exists coincidence of the most appearing time of clinical features of liver cancer at different longitude and latitude, according to the law of field equation and the theory of warpage of space time by Einstein.
METHODSThree regions with different longitude and latitude were selected randomly and sampled. There were 36 items altogether, including 12 clinical items, which were used to imitate the yearly cycle cosine curve. The acorphases and the ratioes of amplitudes and means were compared to justifying whether they were in the same range.
RESULTSAll the acorphases of 36 items appeared between -90.1degrees to -207.5 degrees (from april to july), existing in one third of the same range, in which 13 items occurred rhythmly (P<0.05). The image acorphases of liver cancer at the early and middle stage and gamma-glutamyl transpeptidase acorphase appeared between -98.5 degrees to -148.2 degrees (from april to may), in which 5 items occurred rhythmly (P<0.05).
CONCLUSIONIt is the same mode of the yearly biologcal cycle for liver cancer malignant growth within the most appearing time (from april to july). It will increase the detecting rate of liver cancer at the early and middle stage during this time (especially from april to may).
Carcinoma, Hepatocellular ; pathology ; Cell Cycle ; physiology ; Chronobiology Phenomena ; Hepatocytes ; physiology ; Humans ; Liver Neoplasms ; pathology ; Mathematical Computing ; Periodicity
5.Relationship between sinusoidal endothelial cell apoptosis and hepatocyte injury after their transplantation into rats.
Jin ZHU ; Jia-hong DONG ; Ping CHEN ; Shi-zhong YANG ; Yu-jun ZHANG
Chinese Journal of Hepatology 2006;14(2):114-117
OBJECTIVESTo investigate the relationship between the apoptosis of sinusoidal endothelial cells (SEC) and the hepatocyte injury of the livers after their transplantation into rats.
METHODSMale SD rats were divided into three groups randomly: sham group, UW1h group and UW12 h group. Orthotopic liver transplantations were performed using the technique described by Kamada with a modification. A survival rate curve was made using the Kaplan-Meier method. Liver tissue specimens and blood samples were collected at different time points after the surgeries. Six animals were sacrificed at each time-point. The liver injury was evaluated by serum ALT and HA levels. The incidence of apoptosis in SECs was measured using the Tunel method. Additionally, the typical morphology indication of apoptosis was observed by transmission electron microscopy.
RESULTSThe survival rate at 168 h in the UW12 h group was significantly lower than that in the UW1h group (F = 6.39, P<0.05). The levels of serum ALT and HA were significantly higher in UW12 h group than those in UW1h group (F = 3.99, P<0.05; F = 12.43, P<0.05). The serum ALT level reached its peak at 6 h after transplantation in both groups. The AI of SEC was significantly higher in the UW12 h group than those in the UW1h group and sham group (F = 63.58, P<0.01; F = 86.58, P<0.01). The apoptosis index (AI) in the UW1h group and in the UW12 h group both reached their peak at 6 h postoperatively and the AI of SEC of each group was positively correlated with their serum ALT levels significantly (r = 1.0, P,0.01; r = 0.962, P<0.05).
CONCLUSIONThe increase of apoptosis of SEC is significantly correlated with the dysfunction of the livers after transplantation in rats, and the dysfunction was mainly caused by the process of cold preservation/reperfusion injury.
Animals ; Apoptosis ; physiology ; Cryopreservation ; Endothelial Cells ; pathology ; Hepatocytes ; pathology ; Kupffer Cells ; pathology ; Liver ; pathology ; Liver Transplantation ; adverse effects ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; pathology
6.Immediate postoperative color Doppler ultrasonography on the diagnosis of hemorrhagic complications of liver biopsy and its directed compression hemostasis.
Guo Quan ZHANG ; Ling Yun ZHANG ; Guo Qing HAN ; Yu Hua ZHU ; Ai Min ZHENG
Chinese Journal of Hepatology 2022;30(3):285-289
Objective: To study the diagnostic value of immediate color Doppler ultrasonography on traumatic hepatic hemorrhage after tissue sampling with ultrasound-guided liver biopsy and the clinical effect of its-directed local compression hemostasis at puncture-site. Methods: 132 hospitalized patients with various liver diseases underwent ultrasound-guided hepatic puncture-biopsies, including 61 cases with diffuse parenchymal and 71 cases with focal liver lesions. Immediate postoperative color Doppler ultrasonography was performed following liver biopsy. Abnormal blood flow signal was observed at hepatic puncture biopsy site, and if there were hemorrhagic signals, ultrasound-directed local compression hemostasis was performed until the bleeding signal disappeared. F-test and Chi-square test were used for statistical analysis. Results: Immediate color Doppler ultrasonography showed traumatic hemorrhage in 36.1% (22/61) and 40.8% (29/71) cases of diffuse liver disease and focal liver disease group, respectively. All hemorrhagic signals were eventually disappeared after ultrasound-directed local compression hemostasis. The median hemostasis time was 2 min in both groups, and there was no statistically significant difference in bleeding rate and hemostasis time between the two groups (P>0.05). There were no serious complications and deaths. Conclusion: Traumatic hepatic hemorrhage along the needle puncture tract is a common accompanying condition during liver biopsy. Immediate postoperative color Doppler ultrasonography can trace bleeding signals in timely manner and direct effective compression hemostasis, so it should be used routinely to help avoid occurrence of severe hemorrhagic complications.
Biopsy
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Hemorrhage/etiology*
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Hemostasis/physiology*
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Humans
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Liver/pathology*
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Liver Diseases/pathology*
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Ultrasonography
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Ultrasonography, Doppler, Color/adverse effects*
7.Laminin and its alpha 6 integrin receptor in the regulation of human hepatocellular carcinoma cell phenotypes.
Tian-jing LU ; Qing-yun ZHANG ; Rou-li ZHOU
Chinese Journal of Oncology 2003;25(1):31-35
OBJECTIVETo study the role of integrin alpha 6 in cell attachment, spread, survival/proliferation and differentiation of human hepatocellular carcinoma (HCC) BEL-7402 cells on various substrates by monoclonal antibody against the extracellular domain of alpha 6 subunit (IA6ED McAb).
METHODSThe effect of McAb on attachment and spread of BEL-7402 cells on LN or FN substrate was examined. MTT analysis was used to examine the cell survival/proliferation, gelatin zymography to the matrix metalloproteinases (MMPs) secreted by BEL-7402 cells, and microparticle immunoabsorbent kit to AFP secretion while the cells were cultured on LN-, FN- or Matrigel-coated substrates.
RESULTSThe cell attachment, spread and survival/proliferation were inhibited. Moreover importantly, the malignant cell dedifferentiation and abnormal differentiation on LN-coated substrate were also strongly inhibited by IA6ED McAb.
CONCLUSIONLN and integrin alpha 6 regulate human HCC cell phenotypes of survival/proliferation and differentiation. The phenotypes of dedifferentiation and abnormal differentiation can be reversed by blocking the interaction between integrin alpha 6 and LN using IA6ED McAb, which may lower metastatic potency of tumor cells.
Antibodies, Monoclonal ; pharmacology ; Carcinoma, Hepatocellular ; pathology ; Cell Adhesion ; drug effects ; Humans ; Integrin alpha6 ; immunology ; physiology ; Laminin ; physiology ; Liver Neoplasms ; pathology ; Phenotype ; Receptors, Laminin ; physiology ; Tumor Cells, Cultured
8.Molecular study of the hepatic inflammation to fibrosis to cancer axis.
Chinese Journal of Hepatology 2009;17(10):799-800
Animals
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Carcinoma, Hepatocellular
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etiology
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pathology
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Hepatic Stellate Cells
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metabolism
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pathology
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Hepatitis
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complications
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pathology
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Humans
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Liver
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metabolism
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pathology
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Liver Cirrhosis
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etiology
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pathology
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Liver Neoplasms
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etiology
;
pathology
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Myeloid Differentiation Factor 88
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physiology
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NF-kappa B
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physiology
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Signal Transduction
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Toll-Like Receptor 4
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physiology
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Transforming Growth Factor beta
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physiology
9.A Case of Neck Abscess Caused by Salmonella Serotype D in a Patient with Liver Cirrhosis.
Mee Hye KWON ; Mi Il KANG ; Ji Young CHUN ; Hyun Woo LIM ; Yoon Sik YEUM ; Young Woo KANG ; Young Jin KIM ; Young Keun KIM
Yonsei Medical Journal 2010;51(1):128-130
Non-typhoidal salmonellosis, which is increasing nowadays in Korea as well as in the developed countries, is manifested as enteritis in most cases, but it also encompasses bacteremia, intraabdominal infections, and bone, joint and soft tissue infections. These rare diseases are known to result from primary gastrointestinal infection and subsequent bacteremia with or without symptoms. We experienced a case of neck abscess caused by Salmonella serotype D, which is a rare but important differential diagnosis of neck abscess. We herein report it.
Abscess/*diagnosis/*microbiology
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Aged
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Female
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Humans
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*Liver Cirrhosis
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Neck/*microbiology/*pathology
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Salmonella/*physiology
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Salmonella Infections/*complications
10.Study of ultrasound attenuation during HIFU propagation in ox liver.
Faqi LI ; Jin BAI ; Zhibiao WANG ; Ping MA ; Yonghong DU ; Feng WU ; Ruo FENG
Journal of Biomedical Engineering 2003;20(4):675-678
Ultrasound attenuation has been measured during HIFU propagation in fresh ox liver at different frequency using a radiation force method. The acoustic radiation force was measured before and after the prepared ox liver of various thicknesses (20 mm, 40 mm, 60 mm, 80 mm) which were put into degassed water and exposed to different transducer surface output acoustic powers at a room temperature (20 degrees C) with therapeutic transducers of various frequencies, and then the ultrasound attenuation coefficient was calculated. With the use of therapeutic transducer 4, the focus of the ultrasonic beam was set to be 20 mm, 40 mm or 60 mm deep into the tissue surface using B-mode ultrasound guidance. A single exposure was performed with focal intensity ISATA = 22.0 x 10(3) W/cm2(ISATA, in degassed water) and exposure time 5 sec. The sample was cut after treatment to measure the volume of coagulative necrosis. For a specific therapeutic transducer, the radiation force ratio in liver of constant thickness is independent of the transducer surface sound intensity and the area of the ultrasound window at the sample front face. The radiation force ratio and the volume of coagulative necrosis induced by HIFU are plotted as the functions of sample thickness (or exposed depth), in which it can be seen that these two parameters have the same exponential dependence on sample thickness. The ultrasound attenuation coefficient alpha in ox liver is shown to be frequency f dependent, it almost linearly increases with frequency t. This work shows that such a study is feasible, and offers experimental data that will be useful for future HIFU dosage studies.
Animals
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Cattle
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In Vitro Techniques
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Liver
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pathology
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physiology
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Radiation
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Transducers
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Ultrasonic Therapy
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methods
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Ultrasonics