OBJECTIVETo investigate the protective effect of overexpressed heme oxygenase-1 (HO-1) in hypoxia and the correlation between HO-1 overexpressoin and hypoxia inducible factor-1alpha (HIF-1alpha) in human hepatoma HepG2 cells.

METHODSThe expressions of HO-1 and HIF-1alpha mRNA as well as the protein were detected by RT-PCR and Western blotting, respectively. MTT assay was used to examine the relative cell survival rate. The total superoxide dismutase (SOD) activity was examined with a SOD kit.

RESULTSHypoxia induced overexpression of HO-1 gene in HepG2 cells at transcriptional and translational levels. The relative survival rate of HepG2 cells under hypoxia was significantly decreased after the HO-1 protein overexpression was inhibited by ZnPPIX (P < 0.01). The total SOD activity of cells was significantly increased after cells were treated by hypoxia for 16 hours (P < 0.05), while decreased significantly by HO-1 inhibitor ZnPPIX treatment (P < 0.01). HIF-1alpha was upregulated under hypoxia. In addition, the HO-1 overexpression under hypoxia was decreased by HIF-1alpha inhibitor, while the HIF-1alpha expression level under hypoxia was not significantly changed after HO-1 expression was inhibited by ZnPPIX.

CONCLUSIONThe overexpression of HO-1 in hypoxic HepG2 cells is HIF-1alpha-dependent or at least partly HIF-1alpha-dependent. The relative survival rate of hypoxic hepatoma cells was significantly decreased by HO-1 inhibitor treatment. The results of this study may offer new thought and drug target for the therapy of human hepatoma in the future.

Cell Hypoxia ; Cell Survival ; Heme Oxygenase-1 ; antagonists & inhibitors ; metabolism ; Hep G2 Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Protoporphyrins ; pharmacology ; RNA, Messenger ; metabolism ; Superoxide Dismutase ; metabolism

Objective To explore the changes of structure and function of mitochondria in liver tissue of mice with acute liver injury induced by volatile oils from ArtemisiaeArgyi Folium(VOAAF).Methods VOAAF was obtained by hydrodistillation extraction.specific pathogen free (SPF) Institute of Cancer Research (ICR) mice in half male and half female were randomized into five groups,including control group(n =10),model (carbon tetrachloride,CCl4) group (n =10),low dose (1.9 g · kg-1,n=10),middle dose (2.3 g · kg-1,n =10),and high dose(2.7 g· kg-1,n =12) VOAAF group(test group).The biological samples were obtained in 6 h after gavaging equal volume (20 mL · kg-1) drugs or solvent to mice at single dose.Aspartate transaminase (AST) in serum was detected.Morphological change of mitochondria in hver tissue was observed by transmission electron microscope.Change of mitochondrial membrane potential in liver tissue was examined by JC-1.Change of mitochondrial swelling sensibility in liver tissue was observed by spectrophotometer.Activity change of Na +-K +-ATPase,Ca2+-ATPase and Ca2+-Mg2+-ATPase in liver tissue were detected by phosphorus determination method.Results The levels of AST in control group and low,middle,high dose test group were (154 ± 27),(224 ±56),(251 ±64),(316 ± 101) U · L-1 (P ＜0.05).The mitochondria got swollen and hydropic in some degree,mitochondrial membrane potemial were 31.35 ±9.14,22.06-6.18,21.34 ±5.99,16.48 ±4.88(P ＜0.05).The mitochondrial swelhng sensibility were (1.43 ±0.69) +10-2,(0.68 ±0.28) ×10-2,(0.40 × ±0.18) + 10-2,(0.26 ±0.10) × 10-2 (P ＜ 0.05).The activity change of Na+-K+-ATPase were 4.40 ± 0.90,2.60 ± 0.60,2.20±0.80,2.10 ±0.80(P ＜0.05).The Ca2 +-ATPase were 4.20 ±0.80,2.70 ±0.50,2.50 ±0.80,2.20 ± 0.60 (P ＜ 0.05).The Ca2 +-Mg2 +-ATPase were 3.90 ± 0.70,2.80 ± 0.60,2.60 ± 0.90,2.50 ± 0.70 (P ＜ 0.05).All changes were related to dose variation trend of volatile oils.Conclusion The disorder of the structure and function of mitochondria could be the mechanism of acute liver injury induced by VOAAF in mice.

OBJECTIVETo explore the effect and mechanism of tagalsin on hepatoma cells.

METHODSThe animal models were established by transplanting H(22) mouse hepatoma cells to mouse liver, and ten days later the mice were randomly divided into five groups: blank group, carmofur positive group and tagalsin groups, including low-dose, middle-dose and high-dose groups. Then medicine or oil was given to the mice by gastric gavage in consecutive 5 days with a 2-days interval as a course of treatment, two courses in all. All mice were killed at 24 hours after medication, and the survival period, ascites conditions, aggressive conditions intra- or extra-liver, weight changes, tumor volume and spleen index of the tumor-bearing mice were observed. Pathological changes of the tumors were examined. Apoptotic factors p53 and Bcl-2 protien and mRNA were detected by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR).

RESULTStagalsin inhibited the hepatoma growth effectively without influencing spleen index to some extent. The tumor inhibition rate of tagalsin low, middle and high dose groups were 17.9%, 63.1% and 71.8%, respectively. Immunohistochemical results showed that the p53 and Bcl-2 protein positive cell counts of the positive control and experimental groups were significantly lower than those of the blank group (P < 0.01). RT-PCR results showed that the p53 mRNA expression was significantly enhanced and Bcl-2 mRNA expression was decreased in the positive control groups and tagalsin treatment groups, especially in the high dose group, compared with those of the blank group (P < 0.05).

CONCLUSIONStagalsin can inhibit the growth of mouse hepatoma cells significantly. The mechanism of its anti-tumor effect may work via up-regulating the wild type p53 gene expression and down-regulating Bcl-2 gene expression and thus regulating tumor cell apoptosis.

Animals ; Body Weight ; drug effects ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Line, Tumor ; Diterpenes ; pharmacology ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Mice ; Neoplasm Transplantation ; Plants, Medicinal ; chemistry ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Random Allocation ; Rhizophoraceae ; chemistry ; Tumor Suppressor Protein p53 ; genetics ; metabolism

OBJECTIVETo observe the central nervous system symptoms and alterations in the blood indicators in rats within a short term after benzene poisoning.

METHODTwenty-four female SD rats were randomized into 4 equal groups to receive intraperitoneal injection of low-, medium- or high-dose benzene (39.05, 78.11, and 234.33 mg/kg, respectively) or peanut oil. Blood samples were taken from the rats via the femoral artery 24 h after the injections for routine blood test and liver and kidney function test.

RESULTSIntraperitoneal injection of benzene at a high dose, but not at a low or medium dose, caused obvious symptoms in the central nervous system. Benzene either at a low or medium dose did not produce obvious changes in routine blood test or liver and kidney function test as compared with the control group, but a high dose resulted in significant changes in WBC, PLT, ALT and AST (P<0.05). Abnormalities in the renal function were found in none of the groups (P>0.05).

CONCLUSIONExposure to high-dose benzene can result in abnormalities in the central nervous system, routine blood indicators and liver function, but does not obviously affect the kidney function in rats.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Benzene ; toxicity ; Blood Cell Count ; Central Nervous System Diseases ; chemically induced ; Female ; Kidney ; drug effects ; Liver ; drug effects ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the local cellular immune response after injection of superantigen, the highly agglutinative staphylococin (HAS), into the tumor bed after ultrasound-guided percutaneous microwave coagulation therapy (PMCT) in the liver cancer patients.

METHODSNinety-two patients with pathologically proven primary liver cancer were divided into two groups: 45 in group A were treated by PMCT alone and 47 in the group B by combined with ultrasound-guided percutaneous injection of highly agglutinative staphylococin (HAS). Before and after PMCT and HAS treatment, the patients underwent ultrasound-guided percutaneous biopsy from the tumor bed and the samples were examined by pathology and immunohistochemistry. The infiltration of CD3+, CD4+, CD57+ and CD68+ lymphocytes in treatment zone was compared between the two groups. Moreover, the infiltrating immunocytes were observed by transmission electron microscopy.

RESULTSOne week after HAS injection, the densities of CD3+, CD4+, CD57+ and CD68+ cells in the group B were 54.50 +/- 18.44, 38.14 +/- 12.44, 33.38 +/- 10.79 and 45.56 +/- 16.53, respectively. All the above mentioned parameters increased significantly in varying degrees compared with that before PMCT or HAS injection (P < 0.05). Four weeks after HAS injection, the density of CD3+, CD4+, CD57+ and CD68+ cells in the group B were 32.67 +/- 10.42, 23.43 +/- 6.99, 18.63 +/- 7.89 and 30.01 +/- 11.05, respectively, still significantly higher than those before PMCT (P < 0.05). Five weeks after PMCT and HAS injection, the densities of CD3+, CD4+, CD57+ and CD68+ cells in the group B were 54.50 +/- 18.44, 38.14 +/- 12.44, 33.38 +/- 10.79 and 45.56 +/- 16.53, versus 32.03 +/- 8.11, 15.67 +/- 8.32, 15.23 +/- 8.26 and 29.67 +/- 11.98 in the group A, respectively, still with a significant difference between the two groups (P < 0.05). A lot of lysosomes, endoplasmic reticulum and mitochondria in the immune cells after injection of HAS were observed by transmission electron microscopy.

CONCLUSIONThe local cellular immunity in liver cancer treatment area can be significantly improved by ultrasound-guided injection of highly agglutinative staphylococin after percutaneous microwave coagulation therapy.

Adult ; Aged ; Antigens, CD ; immunology ; Antigens, Differentiation, Myelomonocytic ; immunology ; CD3 Complex ; immunology ; CD4 Antigens ; immunology ; CD57 Antigens ; immunology ; Electrocoagulation ; methods ; Female ; Humans ; Liver Neoplasms ; pathology ; therapy ; Male ; Microwaves ; therapeutic use ; Middle Aged ; Superantigens ; therapeutic use ; T-Lymphocytes ; immunology

AIM: Accommodation is one of the most important functions of human eye, while its mechanism is still under discussion. This paper aimed to study accommodation mechanism with numerical simulation.METHODS: A simulation model was constructed to study the mechanism of accommodation based on the experimental data derived from published resources. The displacement and pressure are applied on the model to study the deformation of lens during accommodating.RESULTS: The simulation showed that, as the eye was accommodating, the thickness of the lens increased linearly,and the lens diameter decreased linearly. The optical power of the lens increased as the accommodation increased. This result was accord with the public facts in accommodation.Furthermore, the pressure was found to have a great influence on the shape of the lens and the optical power. The lens became thinner and flatter as the pressure increased and the pressure caused a remarkable increase of lens' optical power.CONCLUSION: The outcome of this paper is consistent with the Helmholtz's hypothesis on accommodation to some extent. The analytical model presented in this paper can be used in the theoretical study of the accommodation mechanism of the human lens.

OBJECTIVETo study the effects of benzo[a]pyrene (B[a]P) on capability of learning and memory and the content of amino acid neurotransmitters in hippocampus of rats.

METHODSThirty-two healthy, male SD rats were randomly divided into 4 groups according to their weights after intubated into ventricles: the solvent control group, 2.5, 5.0 and 10.0 mmol/L groups. 10 microl of B[a]P olive oil solutions, of different concentrations 2.5, 5.0 and 10.0 mmol/L, were injected into rats' lateral ventricles, respectively. Rats in the solvent control group were injected into the same volume of olive oil as that in B[a]P group. Rats' capability of learning and memory was tested by Morris water maze. The content of amino acid neurotransmitters in rats' hippocampus were determined by high performance liquid chromatogram with a fluorescence detector.

RESULTSCompared with the controls, the performances of learning and memory of rats decreased significantly in B[a]P treated groups (P<0.01). Levels of glutamate (Glu) were lower significantly in treated groups than that in controls (P<0.01). No significant differences were found in contents of aspartic acid (Asp), glycine (Gly) and aminobutyric acid (GABA) among the four groups.

CONCLUSIONB[a]P can damage rats' spatial learning and memory, and which could be related to decreased contents of excitatory amino acids in hippocampus.

Amino Acids ; metabolism ; Animals ; Benzo(a)pyrene ; toxicity ; Hippocampus ; drug effects ; metabolism ; Male ; Maze Learning ; drug effects ; Memory ; drug effects ; Neurotransmitter Agents ; metabolism ; Rats ; Rats, Sprague-Dawley

Adult ; Aged ; Aged, 80 and over ; Cholecystitis ; complications ; Humans ; Middle Aged ; Shock, Hemorrhagic ; etiology ; physiopathology

OBJECTIVEThe incidence of type 1 diabetes varied in different countries, different nations and different regions. This survey was conducted to clarify the incidence of type 1 diabetes of children in Beijing area between 1997 and 2000, to compare and analyze the difference in incidence of type 1 diabetes between the 2 periods of 1988 - 1996 and 1997 - 2000.

METHODAccording to the criteria of WHO Diabetes Mondial (DIAMOND), data were collected from all the children younger than 15 years of age in Beijing area who had the onset of type 1 diabetes during Jan. 1st, 1997 to Dec. 31st, 2000. Using the capture-recapture methods, 95% confidence intervals of incidence were calculated with Poisson's distribution formula. The significance of differences was tested with Chi-square method.

RESULTSThe incidences of type 1 diabetes during 1997 - 2000 were around 0.76/100 000 to 1.21/100 000. The average yearly incidence was 1.014/100 000 (95% confidence interval was 0.98/100 000 - 1.16/100 000). There was no significant difference in the incidence between 1988 - 1996 and 1997 - 2000, and it showed the same result when the incidences were adjusted by age according to the Chinese population census in 2000 (The incidence was 0.83/100 000 in 1988 - 1996 and 0.86/100 000 in 1997 - 2000, respectively). The incidence was higher in 10 - 14 year-old group than the younger groups (P = 0.002). There was no significant difference between male and female groups, either.

CONCLUSIONSNo significant difference was found between the periods 1988 - 1996 and 1997 - 2000 when the average yearly incidence of type 1 diabetes of children in Beijing was compared. These results were different from the other countries' reports that the incidence of type 1 diabetes was increasing by 3% - 5% per annum. There was no significant difference between male and female groups either and there was a higher incidence of type 1 diabetes in 10 - 14 yr group than the other groups in 1997 - 2000. Although the life-style of Beijing people changed a lot, it didn't affect the incidence of type 1 diabetes in children in this area. But since many people migrated to Beijing from other parts of the country, the changes in constitutive proportions of population might have some impacts on the results of the survey.

Age Factors ; Child ; China ; epidemiology ; Diabetes Mellitus, Type 1 ; epidemiology ; Female ; Health Surveys ; Humans ; Incidence ; Male ; Sex Factors

BACKGROUNDAn increasing incidence of disease caused by nontuberculous mycobacteria (NTM) is being reported. The purpose of this study was to determine the isolation rates of NTM from various clinical specimens, and their antimicrobial susceptibility patterns, over a 4-year period in Shanghai.

METHODSAll NTM isolated between 2005 and 2008 at Shanghai Pulmonary Hospital, a key laboratory of mycobacteria tuberculosis in Shanghai, China, were identified with conventional biochemical tests and 16S rRNA gene sequencing. Antimicrobial susceptibility for all NTM was determined using the BACTEC MGIT 960 system.

RESULTSA total of 21,221 specimens were cultured, of which 4868 (22.94%) grew acid fast bacilli (AFB), and 248 (5.09%) of the AFB were NTM. The prevalence rate of NTM was determined as 4.26%, 4.70%, 4.96% and 6.38% among mycobacteria culture positive samples in years 2005, 2006, 2007 and 2008 respectively. These data indicated that the prevalence rate has continuously increased. Sixteen different species of NTM were identified, the most commonly encountered NTM in Shanghai were M. chelonae (26.7%), followed by M. fortuitum (15.4%), M. kansasii (14.2%), M. avium-intracellulare complex (13.1%) and M. terrae (6.9%). The rare species identified were M. marinum, M. gastri, M. triviale, M. ulcerans, M. smegmatis, M. phlci, M. gordonae, M. szulgai, M. simiae, M. scrofulaceum and M. xenopi. The five most commonly identified NTM species showed high drug resistance to general anti-tuberculosis drugs, particularly, M. chelonae and M. fortuitum appear to be multi-drug resistance.

CONCLUSIONSThe prevalence of NTM in Shanghai showed a tendency to increase over the course of the study. The five most commonly isolated NTM species showed high drug resistance to first line anti-tuberculosis drugs.

Antitubercular Agents ; pharmacology ; China ; epidemiology ; Drug Resistance, Bacterial ; Mycobacterium ; drug effects ; physiology ; Mycobacterium Infections ; epidemiology ; microbiology ; Mycobacterium chelonae ; drug effects ; physiology ; Mycobacterium fortuitum ; drug effects ; physiology ; Mycobacterium kansasii ; drug effects ; physiology ; Mycobacterium marinum ; drug effects ; physiology ; Mycobacterium xenopi ; drug effects ; physiology ; Nontuberculous Mycobacteria ; drug effects ; physiology ; Prevalence