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Biomedical subjects

Li Zhang

Publications and source records attributed to Li Zhang.

718 records · Page 40Linked to original sources
PubMed2002

Expressions of vascular endothelial growth factor in cirrhotic tissues and their relations to proto-oncogene c-fos, c-myc.

OBJECTIVE: To investigate the significance of vascular endothelial growth factor (VEGF) in the pathogenesis of liver cirrhosis and the correlation between VEGF and proto-oncogene c-fos and c-myc in cirrhotic liver. METHODS: The proteins of VEGF, c-fos, and c-myc were identified immunohistochemically in each tissue section of 53 cases of liver cirrhosis. The correlations between VEGF, c-fos and c-myc were analyzed. The levels of VEGF protein in different Child gradings were also compared. RESULTS: The proteins of VEGF were more highly expressed in Child A and B patients than in Child C patients and controls. The expressions of both c-fos and c-myc were not statistically significant between VEGF positive and negative patients. CONCLUSIONS: The protein level of VEGF can reflect the compensation status of cirrhosis patients and may act as an anti-cirrhotic factor. The proto-oncogene c-fos, c-myc and VEGF may have different mechanisms in the course of cirrhosis or hepatic tumorigenesis.

Adolescent↗
PubMed2001

Expression of Human Angiostatin in Pichia pastoris and the Detection of Its Anti-angiogenic Activity.

Human angiostatin cDNA was amplified from human hepatoma cell line HepG2 using RT-PCR and was cloned into pPIC9K vector. Recombinant Pichia pastoris strain with 4 copies of angiostatin gene was obtained. Recombinant protein was purified by lysine-affinity Sepharose column and the finally purified angiostatin was 25 mg/L, higher than previously reported 17 mg/L. Amino acid sequence analysis revealed the identity of our protein the same with that previously reported. Recombinant angiostatin inhibited specifically the proliferation of bovine aortic endothelial cell stimulated by bFGF, with ED(50) being about 3 mg/L.

Journal Article↗
PubMed2000

Pharmacokinetics of traditional Chinese syndrome and recipe: a hypothesis and its verification (I).

AIM:To propose a hypothesis defining the absorption, distribution, metabolism and elimination of traditional Chinese recipe (TCR)component in blood of healthy subjects and patients, and estimate its correctness.METHODS:The pharmacokinetics (PK) of same dose of drug was studied in the animal model of traditional Chinese syndrome (S)and healthy animals. The classification, termi-nology, concept and significance of the hypothesis were set forth with evidence provided in the present study. The hypotheses consisted of traditional Chinese syndrome PK (S-PK) and traditional Chinese recipe PK (R-PK). Firstly, the observed tetramethylpyrazine (TMP) PK in healthy, chronically reserpinized rats (rat model of spleen deficiency syndrome, RMSDS) and RMSDS treated with Sijunzi decoction (SJZD) for confirmation were used to verify S-PK; secondly, the ferulic acid (FA) PK in healthy and high molecular weight dextran (HMWD)-induced rabbit model with blood stasis syndrome (RDBSS) was also used to verify S-PK; and lastly, TMP PK parameters in serum of healthy rats after orally taken Ligusticum wallichii (LW), LW and Salvia miltiorrhiza (LW&SM) decoctions were compared to verify R-PK.RESULTS:The apparent first-order absorption Ka,(13.61 plus minus 2.56)h(-1) ,area under the blood drug concentration-time curve AUC, (24.88 plus minus 9.76)&mgr;gcenter doth(-1)mL(-1) , maximum drug concentration C(max), (4.82 plus minus 1.23)&mgr;gcenter dotmL(-1) of serum TMP in RMSDS were increased markedly(P< 0.05) compared with those Ka = (5.41 plus minus1.91)h(-1), AUC = (5.20 plus minus 2.57)&mgr;gcenter doth(-1)center dotmL(-1), C(max) = (2.33 plus minus 1.77)&mgr;gcenter dotmL(-1) of healthy rats (HR). The apparent first-order rate constant for alpha and beta distribution phase alpha = (0.38 plus minus 0.09)h(-1), beta = (0.06 plus minus 0.03)h(-1) , the apparent first-order intercompartmental transfer rate constants K10 = (0.24 plus minus 0.07)h(-1), K(12) = (0.11 plus minus 0.02)h(-1), K(21) = (0.11 plus minus 0.02)h(-1) of serum TMP in RMSDS were decreased significantly (P <0.01) compared with those K(10) = (0.88 plus minus 0.20)h(-1), K(12) = (1.45 plus minus 0.47)h(-1), K(21) = (0.72 plus minus 0.22)h(-1) of HR. However, no apparent differences occurred between HR and RMSDS treated with SJZD. The serum FA concentration and its AUC (5.6690 plus minus 2.3541)&mgr;gcenter doth(-1)center dotmL(-1) in RMBSS were also higher than those AUC =(2.7566 plus minus0.8232)&mgr;gcenter doth(-1)center dotmL(-1) of healthy rabbits (P <0.05). The Ka (11.51 plus minus 2.82)h(-1), AUC (0.84 plus minus0.17)&mgr;gcenter doth(-1)center dotmL(-1) of LW & SM-derived TMP in serum were much lower (P <0.05) than those Ka = (19.58 plus minus 4.14)h(-1),AUC = (1.27 plus minus 0.26)&mgr;gcenter doth(-1)center dotmL(-1) of LW-derived TMP in serum after oral decoctions.CONCLUSION:The SDS and blood stasis syndrome state could affect significantly the pharmacokinetic parameters of drugs and the abnormal SDS pharmacokinetic parameters could be normalized by SJZD. The combination of Chinese medicine in TCR could reciprocally affect the pharmacokinetic parameters of other components absorbed into the systemic circulation. These results support the S and R-PK hypothesis.

Journal Article↗
PubMed1998

CEA and AFP expression in human hepatoma cells transfected with antisense IGF-I gene.

AIM:To determine whether antisense insulin-like growth factor-I(IGF-I) gene can modulate CEA and AFP expression in human hepatoma cells (HepG2).METHODS: Transfection of HepG2 cells was accomplished using Lipofectin reagent. Northern blot analysis confirmed the antisense IGF-I RNA of the transfected cells. CEA and AFP levels were measured using radioimmunoassay.RESULTS: Human hepatoma cell lines (HepG2) were transfected with antisense IGF-I gene. Northern blot analysis confirmed that antisense IGF-I RNA was expressed in the transfected cells. The effect of antisense IGF-I gene on CEA and AFP expression was demonstrated by the fact that the CEA and AFP levels in the supernatant of transfected cell culture were significantly lower as compared with the parent cells, (CEA 7.0&mgr;g/L plus minus 0.76&mgr;g/L and 3.29&mgr;g/L plus minus 1.80&mgr;g/L (P < 0.05) and AFP 53.63&mgr;g/L plus minus 6.02&mgr;g/L and 9.0&mgr;g/L plus minus 5.26&mgr;g/L (P<0.01), respectively).CONCLUSION: The malignant potentiality of the transfected cells was partially suppressed.Antisense IGF-I gene can modulate the expression of CEA and AFP in human hepatoma cell lines (HepG2)

Journal Article↗
PubMedDate not supplied

Quantitative structure-activity relationship for cyclic imide derivatives of protoporphyrinogen oxidase inhibitors: a study of quantum chemical descriptors from density functional theory.

This study examined the applicability of various density functional theory (DFT)-based descriptors, such as energy gap (DeltaE) between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), weighted nucleophilic atomic frontier electron density (WNAFED, FNi), mean molecular polarizability (alpha), and net atomic charge (Qi), in quantitative structure-activity relationship (QSAR) studies on a class of important protoporphyrinogen oxidase (Protox) inhibitors including a series of cyclic imide derivatives with various heterocyclic rings and substituents. Our QSAR analysis using the quantum chemical descriptors calculated at the B3LYP/6-31G(d,p) level led to a useful explicit correlation relationship, i.e. pI50 = -5.7414 + 0.1424alpha - 0.0003alpha2 - 0.4546FNC* + 0.2974QN** (n=26, R2=0.87), showing that descriptors mean molecular polarizability, alpha, and WNAFED FNC* of a critical carbon atom and net atomic charge (Qi) in the molecules are most likely responsible for the in vitro biological activity of cyclic imides. It has been shown that the use of the DFT-based quantum chemical descriptors indeed led to a better QSAR equation than that obtained from the use of the corresponding descriptors calculated at a semiempirical PM3 level. The present work demonstrates that the DFT-based quantum chemical descriptors are potentially useful in the future QSAR studies for quantitatively predicting biological activity, and, therefore, the DFT-based QSAR approach could be expected to help facilitate the design of additional substituted cyclic imide derivatives of Protox inhibitors with the potentially higher biological activity.

Computer Simulation↗
PubMedDate not supplied

Interactions of aryloxyphenoxypropionic acids with sensitive and resistant acetyl-coenzyme a carboxylase by homology modeling and molecular dynamic simulations.

Acetyl-coenzyme A carboxylase (ACCase) has been identified as one of the most important targets of herbicides. In the present study, we constructed homology models of the carboxyl-transferase (CT) domain of ACCase from sensitive and resistant foxtail and used these models as templates to study the molecular mechanism of herbicide resistance and stereochemistry-activity relationships of aryloxyphenoxypropionates (APPs). In the homology modeling structures, the dimer of the CT domain was formed by the side-to-side arrangement of the two monomers, in such a way that the N domain of one molecule is placed next to the C domain of the other. The dimeric association of sensitive foxtail CT was found to differ from that of resistant foxtail CT, and the spatial orientation of two key residues, Leu-695 and Ile-695, in these dimers also differed. The mutation of Ile to Leu may perturb the conformation of the dimeric interface, which may account for the molecular mechanism of herbicide resistance. Further docking analysis indicated that the binding model of high-active compounds is similar to that in the crystal structure of the enzyme-ligand complex. The different spatial orientations of ester groups of the isomers of APPs may explain the stereochemistry-activity relationship. Ser-698 formed a H-bonding interaction with all of the docked ligands, while Tyr-728 formed a pi-pi stacking interaction with some of the APPs. These findings may enhance our understanding of the molecular mechanism of herbicide resistance and stereochemistry-activity relationships, which may provide a new starting point for the identification of more potent inhibitors against both sensitive and resistant ACCase.

Acetyl-CoA Carboxylase↗
PubMedDate not supplied

Proteomics of bovine mitochondrial RNA-binding proteins: HES1/KNP-I is a new mitochondrial resident protein.

Proteomic analysis of bovine mitochondrial proteins with affinity to polyAdenylate or polyUridylate was performed in an effort to identify novel RNA-binding mitochondrial proteins. We have used 2D gel electrophoresis and MALDI-QqTOF mass spectrometry to identify a total of 64 proteins, of which 51 have defined mitochondrial function including 6 known RNA-binding proteins. HES1/KNP-I from the polyA-binding fraction of mitochondrial Triton extract showed exclusive mitochondrial localization when expressed in GFP-tagged form. The HES1/KNP-I gene is on human chromosome 21q22.3 and may be involved in several disorders mapped to that region. Thus, HES1/KNP-I is a proven mitochondrial resident protein with apparent tight membrane association and tentative RNA-binding properties.

Animals↗
PubMedDate not supplied

An investigation on liver-targeting microemulsions of norcantharidin.

Based on the clinical fact that norcantharidin (NCTD) injection frequently causes urinary organ damnification, we prepared a NCTD w/o microemulsion as an alternative to improve the solubility and enhance the live uptake of NCTD. The optimal microemulsion formulation consisted of 7% water, 45% soybean lecithin/ethanol (2:1), and ethyl oleate, with the droplet size of 44.5 +/- 8.6 nm. Pharmacokinetics study showed that NCTD microemulsion had relatively longer circulating time in mice than NCTD injection after a single intravenous injection at a dose of 5 mg/kg. Moreover, the overall drug targeting efficiency of liver was enhanced from 3.66% to 6.10%. These results suggest that a NCTD microemulsion system is a promising candidate for the treatment of hepatogenic diseases.

Animals↗
PubMedDate not supplied

Effects of tibolone and conventional hormone replacement therapies on arterial and hepatic cholesterol accumulation and on circulating endothelin-1, vascular cell adhesion molecule-1, and E-selectin in surgically menopausal monkeys.

OBJECTIVE: Menopause and aging are associated with a marked increase in the incidence of coronary heart disease as well as reductions in circulating estrogen, progestogen, and androgen levels. The synthetic compound tibolone and its metabolites have estrogenic, progestogenic, and androgenic characteristics. In the present study, we compared the effects of tibolone, estrogen replacement therapy, and estrogen plus progestogen replacement therapy on arterial and hepatic lipid accumulation and on circulating soluble adhesion molecule and endothelin-1 concentrations in surgically postmenopausal cynomolgus monkeys. DESIGN: Animals were fed an atherogenic diet for 2 years while receiving either no hormone treatment (control, n = 31) or the following treatments at doses designed to mimic the human dose on a daily caloric intake basis: tibolone at 2.5 mg/day (HiTib, n = 31), tibolone at 0.625 mg/day (LoTib, n = 29), conjugated equine estrogens (CEE) alone at 0.625 mg/day (CEE, n = 29), or CEE plus continuous medroxyprogesterone acetate (MPA) at 2.5 mg MPA/day (CEE + MPA, n = 30). RESULTS: Relative to the control group, iliac artery total cholesterol content was not different in the HiTib, LoTib, and CEE + MPA groups but was significantly lower in the group receiving CEE only (P < 0.05). In contrast, hepatic free cholesterol content was reduced in all treatment groups [HiTib (P < 0.01), LoTib (P < 0.05), CEE (P < 0.01), and CEE + MPA (P < 0.05)], whereas hepatic total and esterified cholesterol content were reduced in the HiTib, CEE, and CEE + MPA groups (all P < 0.05). HiTib and CEE groups had lower hepatic triglyceride levels per milligram of protein (P < 0.05). Iliac arterial cholesterol content was highly correlated with hepatic cholesterol content and with previously published histomorphometrically determined coronary artery atherosclerosis, supporting the use of the iliac artery as a surrogate for the coronary artery in the monkey. Circulating levels of soluble vascular cell adhesion molecule-1 were significantly reduced in the HiTib (P < 0.02) and CEE (P < 0.05) groups, whereas soluble E-selectin was reduced in the CEE group only (P < 0.01). Plasma endothelin-1 was significantly reduced in the LoTib (P < 0.05), CEE (P < 0.01), and CEE + MPA (P < 0.01) groups. CONCLUSIONS: These results suggest that while tibolone caused marked depression of high-density lipoprotein cholesterol and a resultant twofold increase in the total plasma cholesterol/high-density lipoprotein cholesterol ratio, those effects did not result in exacerbation of iliac artery atherosclerosis, perhaps because of beneficial effects on vascular biology or hepatic metabolism.

Androgen Antagonists↗
PubMedDate not supplied

Chronic effects of transmyocardial laser revascularization in the nonischemic myocardium: a word of caution.

BACKGROUND: Transmyocardial laser revascularization (TMLR) has been shown to induce angiogenesis and improve regional myocardial blood flow. However, the biological response to laser of different energy doses in nonischemic myocardium has not been well studied. We study the time course of histological appearance following high- and low-energy TMLR in a rodent model of normal myocardium. METHODS: The animals were randomized to two groups (high-energy (1.4 J/pulse) TMLR group and low-energy (0.6 J/ pulse) TMLR group). TMLR was applied to the anterolateral wall of the left ventricle. Then the animals were sacrificed (one every 2 or 3 days up to 6 weeks, then one every week) to give a series of hearts from 1 week to 12 weeks following TMLR. RESULTS: No patent laser channels were identified. All laser channel remnants were composed of granulation tissue, fibrosis, and various amounts of vascular structures. Changes in vascular density demonstrated a similar pattern in both groups over time. The initial increase in vascular density within the laser channel remnants and the surrounding areas was more marked in group I than in group II. Gradual decline of vascular density occurred during a later follow-up. More fibrosis and less vasculature were demonstrated 12 weeks after laser therapy in group I. CONCLUSION: Angiogenic response to the Holmium:YAG laser in the nonischemic myocardium is nonspecific and unsustainable. TMLR might chronically impair the myocardium function by enhancing regional scar formation. Therefore, we should clearly identify the ischemic area for laser therapy. Reduction of laser energy might prevent this potential complication.

Animals↗
PubMedDate not supplied

Therapeutic angiogenesis for coronary artery disease.

Therapeutic angiogenesis may be a realistic approach in treating ischemic heart disease. VEGF is a major angiogenic factor involved in physiological as well as pathological angiogenesis. The ability of VEGF to promote angiogenesis in animal and clinical studies has been studied extensively. However, it is becoming clear that VEGF alone may not be sufficient to effectively complete the angiogenesis process. The use of more than one growth factor may be more pertinent in creating a sustainable angiogenic effect with clinically significant outcome. The challenge is to find complementary partners in angiogenesis to better affect the outcome of the process. To this end, we have been studying the effects of other angiogenic factors such as angiopoietin-1 (Ang-1) in a chronic ischemic porcine model. Single intramyocardial introduction of adenovirus-mediated gene transfer of Ang-1 into the left ventricle free wall has been found to enhance angiogenesis by augmenting the formation of new capillaries that manifested in improved total blood flow in the myocardium. A combined therapeutic angiogenesis study involving VEGF and Ang-1 is currently underway. Due to their unique complementary properties, it is expected that the combination will not merely enhance angiogenesis but will also lead to healthy and mature vascular network in the ischemic myocardium.

Angiogenesis Inducing Agents↗
PubMedDate not supplied

Influence of medium components on elastase production using crude sources by Bacillus sp. EL31410.

A newly isolated strain EL31410, producing elastase (E.C3.4.4.7) with high elastolytic activity was identified as Bacillus sp. In the medium optimization, it was found that wheat bran and soybean flour hydrosate were the best crude carbon and nitrogen source for enzyme production, respectively. Addition of corn steep flour can affect the bacterium growth and elastase production. A fractional factorial design was applied to study the main factors that affect the enzyme production, and central composite experimental design and response surface methodology were adopted to derive a statistical model for the effect of wheat bran and soybean flour hydrosate on elastase production. The experimental results showed that wheat bran had positive effect but soybean flour hydrosate had negative effect, on enzyme production. An initial concentration of 3.4% (w/v) wheat bran and 9.4% (v/v) soybean flour hydrosate were found to be optimal for enzyme production in batch culture. The time course of elastase production in the optimized medium composition was also described.

Bacillus↗
PubMedDate not supplied

Transient increased expression of VEGF and MMP-1 in a rat liver tumor model after hepatic arterial occlusion.

BACKGROUND/AIMS: This study investigates the influence of hepatic arterial occlusion (HAO) on blood perfusion of transplanted cancer in rat's liver, and the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-1 (MMP-1) and explores the mechanisms involved in transcatheter arterial embolization (TAE)-induced metastasis of liver cancer preliminarily. METHODOLOGY: Walker 256 carcinosarcoma was transplanted into rat's liver to create the liver cancer model. Hepatic arterial ligation (HAL) was used to block the hepatic arterial blood supply and simulate TAE. Rats bearing tumor were divided into three groups: control, laparotomy control, and HAL groups. Blood perfusion of tumor was analyzed by a Hoechst 33342 labeling assay. The level of serum VEGF was assayed by ELISA; and the expression of VEGF and MMP-1 mRNA was detected by in situ hybridization. RESULTS: Two days after HAL, the number of Hoechst 33342 labeled cells which represent the blood perfusion of the tumor directly and hypoxia of tumor indirectly in the HAL group decreased significantly compared with that in the control group (329.1+/-29.3 vs. 383.6+/-19.2, P<0.01). The level of serum VEGF in the HAL group increased significantly compared with that of the control group (92.5+/-43.9 pg/mL vs. 54.9+/-19.3 pg/mL, P<0.05). The expression of VEGF and MMP-1 mRNA in the tumor tissue of the HAL group increased significantly compared with that of the control and the laparotomy control groups (P<0.05). The blood perfusion data of the tumor, represented by number of Hoechst 33342 labeled cells, showed an inverse correlation with the expression of VEGF mRNA in tumor tissue (P<0.05). While 6 days after HAL, the blood perfusion of tumor in HAL group decreased and the expression of VEGF and MMP-1 increased only slightly, not significantly, compared with that in the control group. CONCLUSIONS: In conclusion, blockage of hepatic arterial blood supply results in transient decreased blood perfusion and increased expression of metastasis-associated genes VEGF and MMP-1 of transplanted liver cancer in rats. Decreased blood perfusion and hypoxia may be the major reason for up-regulated expression of VEGF. Better understanding of the mechanisms involved with TAE-induced metastasis may lead to the enhancement of the long-term effects of TAE for liver cancer.

Animals↗
PubMedDate not supplied

Regional portal hypertension diagnosed by ultrasonography: imaging findings and diagnostic values.

BACKGROUND/AIMS: To investigate the diagnostic accuracy of ultrasonography for regional portal hypertension (RPH) and ascertain the best diagnosis method for RPH. METHODOLOGY: Eleven cases of regional portal hypertension diagnosed by ultrasonography were retrospectively studied. Their etiological features, clinical findings, and ultrasonographic diagnosis criteria were analyzed. Other diagnostic approaches were also compared and related literature was reviewed. RESULTS: Eleven patients were all verified by operation. The diagnostic accuracy of color Doppler ultrasonography was 100%. The etiological diagnostic accuracy was 91% (10/11). CONCLUSIONS: Color Doppler ultrasonography should be considered as the first choice to diagnose RPH due to its safety, accuracy, and simplicity. RPH can be classified etiologically into 3 types: pancreatic RPH, splenic RPH, retroperitoneal RPH.

Adult↗