PubMed Health⌕ Search

Biomedical subjects

Jianwen Liu

Publications and source records attributed to Jianwen Liu.

At least 19 recordsLinked to original sources
PubMed2006

Antidiabetic activity of lipophilic (-)-epigallocatechin-3-gallate derivative under its role of alpha-glucosidase inhibition.

(-)-Epigallocatechin-3-gallate (EGCG), a component of catechins, has been shown to reduce blood glucose levels. In the present study, we investigated the antidiabetic activity and its mechanism of lipophilic EGCG derivative (L-EGCGd) in streptozotocin (STZ)-induced diabetic rats. L-EGCGd was chemically modified from traditional hydrophilic EGCG. After 30 days treatment, plasma levels of glucose were significantly reduced by 40.5+/-7.0% and 17.0+/-2.8% in groups administered 50 or 25 mg kg(-1)d(-1) L-EGCGd, respectively, as compared with that in the diabetic control group. Lipid metabolites, such as total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDLC) were effectively attenuated by L-EGCGd administration, but plasma HDLC levels did not change significantly. The oral glucose tolerance test (OGTT) greatly revealed the improved ability of glucose tolerance with treatment of L-EGCGd. L-EGCGd only retarded the postprandial rise in blood glucose with sucrose loading but not glucose loading. And activity of alpha-glucosidase was inhibited by 50% at the concentration of 246.6 microg ml(-1) L-EGCGd. As a result, we first demonstrated that the purified form of compound L-EGCGd possessed the hypoglycemic effect under its role of alpha-glucosidase inhibition, and therefore should be possibly accepted as an alternative oral medication protecting patients against postprandial hyperglycemic toxicity on the treatment of diabetes and its complications.

Animals↗
PubMed2006

Novel fluorescent markers for hypoxic cells of naphthalimides with two heterocyclic side chains for bioreductive binding.

Novel naphthalimides with two heterocyclic side chains of 2-nitroimidazole for bioreductive binding were designed, synthesized, and used as fluorescent markers for hypoxic cells. Their evaluation for imaging tumor hypoxia was carried out in V79 cells, CHO cells, and 95D cells in vitro by using fluorescence scan ascent. A2 and A4 showed a very large differential fluorescence between hypoxic and oxic cells (V79 cells) in vitro and are promising candidate markers for hypoxic cells.

Animals↗
PubMed2006

Synthesis and evaluation of novel 8-oxo-8H-cyclopenta[a]acenaphthylene-7-carbonitriles as long-wavelength fluorescent markers for hypoxic cells in solid tumor.

Novel bioreductive and long-wavelength fluorescent markers for hypoxic cells in solid tumor, 9-isocyano-8H-acenaphtho[l,2-b]pyrrol-8-one with the side chain of 2-nitroimidazole, were designed, synthesized, and evaluated in V79 379A Chinese hamster cells in vitro. Compounds A(2) and A(4) showed good hypoxic-oxic fluorescence differential in vitro (V79 cells) by using fluorescence scan ascent.

Acenaphthenes↗
PubMed2006

Inhibition effect of Oncostatin M on metastatic human lung cancer cells 95-D in vitro and on murine melanoma cells B16BL6 in vivo.

Oncostatin M (OSM) is a multifunctional regulator of cell growth and differentiation. It inhibits the growth of many types of tumor cells, but its role in metastasis is unknown. We studied the human OSM expressed and purified from reconstructed E. Coli on its activity of inhibiting metastasis of tumor cells by a series of assays in vitro and in vivo. Clone formation assay in soft agar was used to measure the inhibition activity of OSM on the proliferation of high metastatic human lung cancer cells 95-D. Cell attachment assay, cell migration assay and cell invasion assay were used to evaluate inhibition by OSM on 95-D cells of the adhesion ability, the migration ability, and the ability of cells to cross tissue barriers, respectively. Inhibition of OSM on secretion of MMP-2 and -9 secretion in 95-D cells was determined by Western blot. The in vivo inhibitory effect of OSM on metastasis of murine melanoma cells B16BL6 was examined in the pulmonary metastasis model. In vitro studies showed that OSM inhibited the proliferation of 95-D cells at low concentration. OSM also reduced the adhesion and invasion ability of 95-D cells and inhibited the secretion of MMP-2 and MMP-9 in OSM treated cells. In vivo results showed that OSM (20 microg/kg/d for 7 days) inhibited pulmonary metastasis at a rate of 20.7%. There were no differences in animal weights among the groups. These results suggest that OSM has the potential of being a clinical inhibitor on metastasis of some cancer cells.

Animals↗
PubMed2005

Patterns of gene expression in the frontal cortex discriminate alcoholic from nonalcoholic individuals.

Alcohol dependence is characterized by tolerance, physical dependence, and craving. The neuroadaptations underlying these effects of chronic alcohol abuse are likely due to altered gene expression. Previous gene expression studies using human post-mortem brain demonstrated that several gene families were altered by alcohol abuse. However, most of these changes in gene expression were small. It is not clear if gene expression profiles have sufficient power to discriminate control from alcoholic individuals and how consistent gene expression changes are when a relatively large sample size is examined. In the present study, microarray analysis (approximately 47,000 elements) was performed on the superior frontal cortex of 27 individual human cases (14 well characterized alcoholics and 13 matched controls). A partial least squares statistical procedure was applied to identify genes with altered expression levels in alcoholics. We found that genes involved in myelination, ubiquitination, apoptosis, cell adhesion, neurogenesis, and neural disease showed altered expression levels. Importantly, genes involved in neurodegenerative diseases such as Alzheimer's disease were significantly altered suggesting a link between alcoholism and other neurodegenerative conditions. A total of 27 genes identified in this study were previously shown to be changed by alcohol abuse in previous studies of human post-mortem brain. These results revealed a consistent re-programming of gene expression in alcohol abusers that reliably discriminates alcoholic from non-alcoholic individuals.

Adult↗
PubMed2005

Reversal of chemical-induced liver fibrosis in Wistar rats by puerarin.

Puerarin is a major isoflavonoid compound isolated from Pueraria lobata, an edible vine used widely for various medicinal purposes. It has been used for centuries in China to counteract alcohol intoxication. However, the effects of puerarin on chemical-induced liver fibrosis have not been reported. In the present study, we investigated the effects of puerarin on liver fibrosis in Wistar rats induced by alcohol plus carbon tetrachloride administration. Liver fibrosis was produced in rats by treatment with a mixture (50% alcohol, 8 g/kg per day; corn oil, 2 g/kg per day; pyrazole, 24 mg/kg per day; ig) once a day and by intraperitoneal injection of 0.25 ml/kg of a 25% solution of carbon tetrachloride in olive oil twice a week for 8 weeks. After 8 weeks, treatment with puerarin (0.4 and 0.8 g/kg ig, daily for 4 weeks) was conducted to examine its therapeutic effects. At the same time, the model group and treatment group continued to receive the chemical mixture, while the control group received saline instead of the chemical mixture. Upon pathological examination, the puerarin-treated rats significantly reversed the symptoms of liver fibrosis and other hepatic lesions. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as indexes of hepatic cell disruption, were reduced with puerarin treatment, whereas no significant effect was discovered in the levels of alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) activities. A significant increase in apoptosis of activated hepatic stellate cell (HSC) was found by flow cytometric analysis of the hepatic tissues. And the expression of bcl-2 mRNA was down-regulated after puerarin administration. Consequently, all these results showed that puerarin could effectively reverse chemical-induced liver fibrosis in experimental rats, via the recovery of hepatic injury as well as the induction of apoptosis in activated HSC.

Alanine Transaminase↗
PubMed2005

Antimetastatic effect of a lipophilic ascorbic acid derivative with antioxidation through inhibition of tumor invasion.

PURPOSE: Ascorbic acid (AA), the natural antioxidant, has been demonstrated to exert an antimetastatic action; however, AA is quite unstable in physiological condition. The aim of the present study is to investigate the stability, the antioxidation and the antimetastatic effects of three lipophilic AA derivatives in vitro as well as in vivo. METHODS: The 95D cells were treated with ascorbic acid-2-O-phosphate-6-O-laureate (AA2P6L), ascorbic acid-2-O-phosphate-6-O-myristate (AA2P6M) and ascorbic acid-2-O-phosphate-6-O-stearate (AA2P6S). AA derivatives' stability in medium under cell culture condition, in the presence and in the absence of 95D cells, was assessed by high-performance liquid chromatography assay. Cell viability and intracellular oxidative stress were measured by MTT assay and CDCFH assay, respectively. Wound healing assay and cell adhesion assay were used to investigate the antimetastatic activities against 95D cells in vitro, and the C57BL/6 mice model was used to evaluate the antimetastatic action in vivo. RESULTS: All the three AA derivatives exhibited excellent stability, significantly different from AA. Results of MTT assay showed that IC(50) values of the cytotoxicity of those AA derivatives, namely AA2P6L, AA2P6M and AA2P6S, were 38.46, 28 and 22.97 microg/ml, while the CDCFH assay indicated that EC(50) values of antioxidant effects on 95D cells were 31.12, 33.51 and 38.31 microg/ml, respectively. Through the ratio of IC(50) vs EC(50) for AA derivatives, AA2P6L was demonstrated to be the most effective AA derivative, which retained the antioxidant ability as well as low cytotoxicity. AA2P6L dose-dependently inhibited 95D cells' migration and adhesion, by 50% at the concentration of 20 and 57 microg/ml, respectively. In the animal experiment, intraperitoneal administration of 75 mg/kg AA2P6L decreased the number of metastatic nodules by 62% and elevated the survival rate of C57BL/6 mice about onefold compared to the control group. CONCLUSION: AA2P6L, a lipophilic AA derivative with antioxidation, is shown to be a potent antimetastatic agent through the inhibition of tumor invasion. These results support future investigations on the feasibility of cancer chemotherapy with AA2P6L.

Animals↗
PubMed2005

Distinct immunosuppressive effect by Isodon serra extracts.

Distinct effect of ent-Kaurene Diterpenoids from Isodon serra on abnormal proliferation of murine lymphocytes was examined with MTT assay and Flow Cytometry Analyses (FCAS). After choosing the most appropriate monomer from these Diterpenoids, we introduced mouse tumescence model to investigate whether it could impact cytokine production in vivo with ELISA assay. The result of MTT assay showed that four ent-Kaurene Diterpenoids could effectively suppress the murine splenic T lymphocytes overproduction stimulated by Concanavalin A, while inhibitive effect was softer on normal sleep lymphocytes than the stimulated ones. Among four ent-Kaurene Diterpenoids, Enmein was the most sensitive one with IC50/EC50 equaling to 1.55. This inhibitive activity was due to interfering DNA replication in G1-S stage and to regulating cell cycle according to flow cytometry analyses (FCAS) result. Xylene-induced mouse tumescence model result further suggested that Enmein depressed the murine ear swelling extent and the level of Interleukin-2 in blood serum in a dose-dependent manner. In conclusion, it demonstrated that four ent-Kaurene Diterpenoids from I. serra had distinct immunosuppressive effect in vitro and in vivo systems, which primarily differentiated Enmein from the others. The experimental results provided insight into a potential immunosuppressive action of Enmein as a promising drug, though profound mechanism remained to be further studied.

Animals↗
PubMed2005

Reversal of multidrug resistance in KB cells with tea polyphenol antioxidant capacity.

Tea polyphenol (TP), (-)-epigallocatechin gallate (EGCG) in particular, were examined for their reversal effects on multidrug resistance (MDR) with their antioxidant capacities. TP and EGCG were proved to exert reversal effects on drug resistance KB-A-1 cells by 5.2 and 2.5 times, respectively, but no such effects were found on drug sensitive KB-3-1 cells. With a redox indicator 6-carboxy-2',7'-dichlorodihydrofluorescein (CDCFH), it could be found that the intracellular reactive oxygen species (ROS) decreased in the KB-3-1 cells, which was induced by different concentrations of doxorubicin, whereas the intracellular ROS induced by doxorubicin in KB-A-1 cells maintained a high level. Such observation suggests that drug resistant cells undergo oxidative stress. Furthermore, this elevated redox level in KB-A-1 cells was inhibited by either TP or EGCG. These results demonstrate that the reversal effect of TP and EGCG on MDR acts, at least in part, regulating the doxorubicin induced intracellular concentration of ROS.

Antioxidants↗
PubMed2005

Repressions of MMP-9 expression and NF-kappa B localization are involved in inhibition of lung carcinoma 95-D cell invasion by (-)-epigallocatechin-3-gallate.

Epigallocatechin-3-gallate (EGCG) repressed the invasion of lung carcinoma 95-D cells in invasion assay. RT-PCR analysis illuminated that 40 microM EGCG down-regulated the expression of MMP-9 by 45.7% and the result of Western blot analysis provided further evidence. NF-kappa B localized in the nucleus of the 95-D cells was diminished in a dose-dependent manner in EGCG-treated cells as shown by Western blot. Intracellular oxidants were more abundant in invasive cells than in invasion-suppressed cells fed with EGCG for 18 h. Thus, the inhibition of tumor invasion by EGCG was shown to be attributed to decreases of the expression of MMP-9 and NF-kappa B, which may result from decrease of intracellular oxidants.

Antioxidants↗
PubMed2005

Modulation effect of tea polyphenol toward N-methyl-N'-nitro-N-nitrosoguanidine-induced precancerous gastric lesion in rats.

The chemopreventive effect of tea polyphenol (TP) on precancerous gastric lesion was examined. A rat model was established by gavage of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and different concentrations of TP were given to Wistar rats in drinking water during the 16 weeks of the experiment. The histopathological data showed an effect of TP to lighten the lesions induced by MNNG. By flow cytometry, we demonstrated that TP treatment decreased the proliferation and apoptosis index (AI) induced by MNNG. The arrest in the G0-G1 phase of the cell cycle was also obtained. The results suggested that TP had preventive effect against gastric carcinogenesis at the preinitiation stage and such prevention may be related to the modulation of the balance of cell death and cell proliferation.

Animals↗
PubMed2005

Ribozyme knockdown of the gamma-subunit of rod cGMP phosphodiesterase alters the ERG and retinal morphology in wild-type mice.

PURPOSE: To generate an animal model of retinal degeneration by using AAV-mediated ribozyme knockdown of the gamma-subunit of the rod cGMP phosphodiesterase (PDEgamma) mRNA in the retina of wild-type mice. METHODS: Two hammerhead ribozymes, HRz35 and HRz42, were designed to target the PDEgamma gene in wild-type C57BL/6 mice. The efficiency and specificity of the ribozyme cleavage was tested in vitro against three different types of target: short synthetic RNA oligomers, longer targets transcribed from clones, and full-length mRNA from total retinal RNA extracts. After in vitro validation, the ribozymes were cloned and packaged in a recombinant adenoassociated virus (rAAV) containing a proximal 472-bp murine rod opsin promoter (MOPS) to drive ribozyme synthesis. Three-week-old wild-type C57BL/6 mice were injected subretinally with the vectors. For treated versus partner control retinas, responses to light were measured by full-field electroretinography (ERG), and retinal tissues were examined by light microscopy. Messenger RNA and protein levels of PDEgamma gene were monitored by reverse transcription-polymerase chain reaction (RT-PCR) and Western immunoblot assay. RESULTS: The ribozymes had comparable in vitro kinetic properties in multiple turnover kinetic analyses. Ribozyme HRz35 exhibited a K(cat) of 0.48 minute(-1) and a K(m) of 980 nM, and HRz42 showed a K(cat) of 0.17 minute(-1) and a K(m) of 971 nM. Both ribozymes cleaved at accessible sites in the RNA, as they digested long transcripts transcribed from clones and full-length mRNA from total retinal RNA extracts in vitro. At increasing intervals after subretinal injection with either AAV ribozyme, a 30% to 90% reduction in a- and b-wave amplitudes was observed compared with those in contralateral control eyes that were not injected. Retinal tissue analysis showed that loss of the photoreceptor cells and PDEgamma mRNA and protein paralleled the ERG results. CONCLUSIONS: Ribozyme-mediated somatic knockdown of wild-type PDEgamma mRNA in vivo can efficiently reduce the target RNA leading to a loss in rod photoreceptors and in rod-mediated ERG amplitudes, thus generating an animal model of retinal degeneration resembling human RP in an essentially normal adult retina. This vector ribozyme technique should be applicable to other genes associated with RP and perhaps also to mRNAs of phototransduction genes not yet associated with RP. Application of this approach may be age and species independent.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2004

A density functional study on nitrogen-doped carbon clusters CnN3- (n=1-8).

Using molecular graphics software, we designed numerous models of CnN3- (n=1-8). Geometry optimization and calculation on vibration frequency were carried out by the B3LYP density functional method. After comparison of structure stability, we found that the structures of ground-state CN3- and C2N3- are bent chains with a nitrogen atom at either end, whereas when n=3-8, the ground-state clusters show three branches, each with a nitrogen atom located at the end. When n=5-8, the longest branch of CnN3- is polyacetylenelike. When n=5 or 7, the longest branch is connected to the central sp2 carbon in a nonlinear manner. The CnN3- (n=1-8) with an even number of carbon atoms are more stable than those with odd numbers, matching the peak pattern observed in laser-induced mass spectra of CnN3-. The trend of such odd/even alternation is explained based on concepts of bonding characteristics, electron affinities, and incremental binding energies.

Journal Article↗
PubMed2004

Antimetastatic effect of prodigiosin through inhibition of tumor invasion.

Prodigiosin, a bacterial metabolite, was reported to have immunosuppressive and anticancer activities. In this study, we investigated novel functions of prodigiosin about anti-metastasis and anti-invasion. Prodigiosin dose-dependently inhibited 95-D cells' migration and invasion according to wound healing assay and the Transwell assay. The inhibitive effect could reach about 50% when cells were treated with 5 microM prodigiosin for 12 h. In animal experiment, intraperitoneal administration of 5 mg kg(-1) prodigiosin decreased the number of metastatic nodules by 53% and elevated the survival rate of mice about one-fold comparing with control group. Results of cell aggregation and adhesion assay showed that prodigiosin could promote cell aggregation and simultaneously inhibit cell from adhering to extracellular matrix (ECM). In addition, prodigiosin suppressed RhoA gene expression, hence, decreased protein level of RhoA in 95-D cells, according to RT-PCR assay and Western blot assay. Gel zymogram assay revealed that prodigiosin could suppress the activity of matrix metalloproteinase-2 (MMP-2). These results demonstrate that prodigiosin effectively inhibit tumor metastasis in vitro and in vivo. The action mechanisms of prodigiosin are associated with the promotion of cell aggregation and the inhibition of various steps in cell invasive process, which include the inhibition of cell adhesion and mobility in a RhoA-dependent way and the suppression of MMP-2 ability.

Animals↗
PubMed2004

In vivo reversal of doxorubicin resistance by (-)-epigallocatechin gallate in a solid human carcinoma xenograft.

A human carcinoma xenograft model was established with resistant KB-A-1 cell line in order to investigate whether (-)-epigallocatechin gallte (EGCG) can reverse doxorubicin (DOX) resistance in vivo. EGCG could sensitize the tumors to DOX as indicated by a considerable reduction of tumor weights. The combination of DOX with EGCG increased the DOX concentration by 51% in the tumors, and increased DOX-induced apoptosis in the tumors compared with DOX alone. In addition, the combination schedules appeared to be well tolerated. We conclude that EGCG could chemosensitize resistant tumor cells to DOX in vivo through an increase in the accumulation of DOX in the tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Ascorbic acid-2-o-phosphate-6-o-palmitate protecting the human umbilical cord vein endothelial cells against hydrogen peroxide and tert-butyl hydroperoxide induced cytotoxicity.

Reactive oxygen species are believed to play a role in the development of several diseases including vascular diseases and the aging process. It is reported that increased reactive oxygen species were implicated as an important mechanism that contributes to endothelial dysfunction. So, human umbilical cord vein endothelial cells were used to study the antioxidative effect of L-ascorbic acid and its derivative. The study indicated that L-ascorbic acid as a traditional antioxidant was instable and could protect the cells against hydrogen peroxide induced cytotoxicity as its concentration below 50 microg/ml, but hardly could protect the cells against tert-butyl hydroperoxide induced cytotoxicity. Ascorbic acid-2-o-phosphate-6-o-palmitate could effectively protect the cells against hydrogen peroxide and tert-butyl hydroperoxide induced cytotoxicity, and exhibited no cytotoxicity within the tested concentration range. The study indicated that ascorbic acid-2-o-phosphate-6-o-palmitate could not only significantly reduce the intracellular reactive oxygen species level in 3 h culture, but also increase the cell viability in 15 h culture. In addition, ascorbic acid-2-o-phosphate-6-o-palmitate could keep stable in RPMI-1640 medium and water for 4 days, permeate the cell membrane, which in turn may scavenge the intracellular reactive oxygen species, increase the cell viability and the plasminogen activators'activity. All the above results suggested that addition of some hydrophobic groups to the traditional antioxidants could form novel compounds with better properties.

Antioxidants↗
PubMed2004

In vitro reversal MDR of human carcinoma cell line by an antisense oligodeoxynucleotide-doxorubicin conjugate.

A conjugate of antisense oligodeoxynucleotide (AS ODN) covalently linked with deoxorubicin (DOX) was synthesized. Its properties and antitumour activity in human carcinoma DOX resistant cells (KB-A-1) were investigated in vitro. The results showed that the conjugate was strongly stable both in Dulbecco's Phosphate-Buffered Saline (PBS) and in culture medium. The intracellular concentration of the conjugate was higher than that of the AS DON by HPLC analysis. The conjugate showed potent dose-dependent inhibition to the growth of KB-A-1 cells. Chemosensitivity of KB-A-1 cells to DOX was also investigated in vitro. When the cells were first exposed to the conjugate (0.5 microM) and then exposed to DOX for 24 h, the IC50 value of DOX decreased from 21.5 to 2.2 microM. In contrast, when treated with the mixture of the same concentration of the AS ODN with equivalent DOX, the IC50 value of DOX was 16.8 microM. Intracellular DOX concentration was detected in KB-A-1 treatment with the conjugate in vitro by HPLC. The results showed that the intracellular DOX concentration was 6.4-fold increased in KB-A-1 cells treated with the conjugate compared to treatment with DOX alone. In contrast, 1.8-fold increasing was observed when treated with the AS ODN. Western blot analysis showed a significantly decrease in the amount of P-glycoprotein in KB-A-1 cells. These results suggest that the conjugate is effective in reversing multidrug resistance. Certainly, further studies are conducting to explore the antitumour effect of the conjugate in vivo.

Cell Line, Tumor↗