Biomedical subjects

B Zhong

Publications and source records attributed to B Zhong.

At least 19 recordsLinked to original sources

PubMed2006

Novel role of Stat1 in the development of docetaxel resistance in prostate tumor cells.

A major obstacle for clinicians in the treatment of advanced prostate cancer is the inevitable progression to chemoresistance, especially to docetaxel. It is essential to understand the molecular events that lead to docetaxel resistance in order to identify means to prevent or interfere with chemoresistance. In initial attempts to detect these events, we analysed genomic differences between non-resistant and docetaxel-resistant prostate tumor cells and, of the genes modulated by docetaxel treatment, we observed Stat1 and clusterin gene expression heightened in the resistant phenotype. In this study, we provide biochemical and biological evidence that these two gene products are related. Stat1 and clusterin protein expression was induced upon docetaxel treatment of DU145 cells and highly overexpressed in the docetaxel-resistant DU145 cells (DU145-DR). The increase in total Stat1 corresponded to an increase in phosphorylated Stat1. Interestingly, there was no detectable difference between DU145 and DU145-DR cells expression of total Stat3 and phosphorylated Stat3. Treatment of DU145-DR cells with small interfering RNA targeted for Stat1 not only resulted in the knockdown of Stat1 expression, but it also caused the inhibition of clusterin expression. Thus, Stat1 appears to play a key role in the regulation of clusterin. Remarkably, inhibition of Stat1 or clusterin expression resulted in the re-sensitization of DU145-DR cells to docetaxel. These results offer the first evidence that Stat1, and its subsequent regulation of clusterin, are essential for docetaxel resistance in prostate cancer. Targeting this pathway could be a potential therapeutic means for intervention of docetaxel resistance.

Antineoplastic Agents, Phytogenic↗

PubMed2005

A matched, case-control study of the association between Schistosoma japonicum and liver and colon cancers, in rural China.

A study of liver and colon cancers and their association with a previous diagnosis of schistosomiasis was performed in rural Sichuan, China. The data analysed came from 127 liver-cancer and 142 colon-cancer patients, each matched, by age, gender, hospital and township, with one or two controls. The cancer cases were identified from the hospital records of three Sichuan counties (all of which have some level of endemic schistosomiasis japonicum): Meishan (66 liver and 54 colon cases), Pujiang (16 liver and 22 colon cases) and Xichang (45 liver and 66 colon cases). Each control was selected using the hospital records for the same year the matched case of cancer was diagnosed, when the control had been found to have an illness other than cancer. Previous schistosomal infection was determined by examining the medical records at the county hospitals, searching the records at the local schistosomiasis-control stations or health-surveillance units, and, when no written record could be found, by interviews with the subjects or their relatives. Given the extremely strong association between hepatitis and liver cancer in China, only data from hepatitis-negative pairs were used in the analyses. Previous schistosomal infection was found to be significantly associated with both liver cancer (odds ratio = 3.7; 95% confidence interval = 1.0-13) and colon cancer (odds ratio = 3.3; 95% confidence interval = 1.8-6.1). The results indicate a fraction of disease attributable to schistosomiasis of 24% for colon cancer, and (among the hepatitis-negative population) one of 27% for liver cancer.

Adult↗

PubMed2003

A minor outer capsid protein, P9, of Rice dwarf virus.

Partial amino acid sequence of a minor 30 kDa polypeptide in purified Rice dwarf virus (RDV) was identical to the deduced amino acid sequence encoded by the dsRNA segment S9 of the virus. This polypeptide was specifically detected by Western blotting analysis with antibodies raised against the product of S9 expressed in a baculovirus system. Treatment of purified RDV particles with a relatively higher concentration of MgCl2 removed the polypeptide from core particles together with other outer capsid proteins. These results demonstrate that the 30 kDa polypeptide is a minor outer capsid protein that is encoded by genome segment S9 of RDV. This protein was named P9 protein.

Amino Acid Sequence↗

PubMed2001

Asymmetric synthesis of chiral organofluorine compounds: use of nonracemic fluoroiodoacetic acid as a practical electrophile and its application to the synthesis of monofluoro hydroxyethylene dipeptide isosteres within a novel series of HIV protease inhibitors.

Two stereoselective routes to a series of diastereomeric inhibitors of HIV protease, monofluorinated analogues of the Merck HIV protease inhibitor indinavir, are described. The two routes feature stereoselective construction of the fluorinated core subunits by asymmetric alkylation reactions. The first-generation syntheses were based on the conjugate addition of the lithium enolate derived from pseudoephedrine alpha-fluoroacetamide to nitroalkene 12, a modestly diastereoselective transformation. A more practical second-generation synthetic route was developed that is based on a novel method for the asymmetric synthesis of organofluorine compounds, by enolate alkylation using optically active fluoroiodoacetic acid as the electrophile in combination with a chiral amide enolate. Resolution of fluoroiodoacetic acid with ephedrine provides either enantiomeric form of the electrophile in > or = 96% ee. Alkylation reactions with this stable and storable chiral fluorinated precursor are shown to proceed in a highly stereospecific manner. With the development of substrate-controlled syn- or anti-selective reductions of alpha-fluoro ketones 44 and 45 (diastereomeric ratios 12:1-84:1), efficient and stereoselective routes to each of the four targeted inhibitors were achieved. The optimized synthetic route to the most potent inhibitor (syn,syn-4, K(i) = 2.0 nM) proceeded in seven steps (87% average yield per step) from aminoindanol hydrocinnamide 40 and (S)-fluoroiodoacetic acid, and allowed for the preparation of more than 1 g of this compound. The inhibition of HIV-1 protease by each of the fluorinated inhibitors was evaluated in vitro, and the variation of potency as a function of inhibitor stereochemistry is discussed.

Anti-HIV Agents↗

PubMed2001

Cooperative regulation of Mcl-1 by Janus kinase/stat and phosphatidylinositol 3-kinase contribute to granulocyte-macrophage colony-stimulating factor-delayed apoptosis in human neutrophils.

Polymorphonuclear neutrophils (PMN) are phagocytic cells constitutively programmed for apoptotic cell death. Exposure to GM-CSF delays apoptosis as measured by annexin-V staining and cell morphological change. We found that STAT5B, STAT1, and STAT3 DNA-binding activity was induced by GM-CSF. We also detected activation of the phosphatidylinositol 3-kinase (PI 3-kinase) pathway after GM-CSF treatment which was inhibited by treatment with the PI 3-kinase inhibitors, wortmannin and LY294002. We investigated whether STAT or PI 3-kinase activity was necessary for the pro-survival response of GM-CSF in PMN. Exposure of PMN to GM-CSF in the presence of either AG-490, antisense STAT3 oligonucleotides, or wortmannin resulted in a partial inhibition of GM-CSF-mediated pro-survival activity. GM-CSF induced a time-dependent increase in the mRNA and protein expression of the anti-apoptotic Bcl-2-family protein, Mcl-1. We examined the hypothesis that Janus kinase/STAT and PI 3-kinase regulation of Mcl-1 contributed to GM-CSF-delayed apoptosis. Using either AG-490 or wortmannin alone, we observed a dose-dependent inhibition of GM-CSF-induced Mcl-1 expression. Using suboptimal doses of AG-490 and wortmannin, we found that both drugs together had an additive effect on delayed apoptosis and Mcl-1 expression. These data suggest that cooperative regulation of Mcl-1 by the Janus kinase/STAT and PI 3-kinase pathways contribute to GM-CSF-delayed apoptosis.

Apoptosis↗

PubMed2001

Epstein-Barr virus infection of sinonasal lymphoepithelial carcinoma in Guangzhou.

OBJECTIVES: To investigate the prevalence of sinonasal lymphoepithelial carcinoma (SNLEC) in Guangzhou, a high incidence area of nasopharyngeal carcinoma (NPC), and to detect whether it is associated with Epstein-Barr virus (EBV) infection. METHODS: Twenty confirmed SNLEC specimens were collected from all of the sinonasal carcinoma biopsies performed in the 8 years 1989-1996 at the Sun Yat-sen University of Medical Sciences. EBV encoded early RNAs were detected by use of in-situ hybridization. A variety of antigens, including the EBV nuclear antigen 1, latent membrane protein 1, BZLF1 protein, diffuse early antigen, viral capsid antigen and membrane antigen, were detected using immunohistochemistry. Additionally, 36 NPC specimens were used for comparison. RESULTS: Twenty SNLECs were identified. Seventeen SNLECs were developed in the nasal cavity, and 3 in the maxillary sinus. The mean age (46.25 y), male to female ratio (3:1), histopathology and lymphoinfiltration of the 20 SNLECs were identical with those of the 36 NPCs. Thirteen (65.0%) of the 20 SNLECs showed an expansive growth pattern, while 27 (75.0%) of the 36 NPCs showed an infiltrating or mixed growth pattern. The majority of cancer cells in all of the 20 SNLECs showed EBV encoded early RNAs. The EBV nuclear antigen 1 expression of SNLEC was less intensive than that of NPC. The expression rate of latent membrane protein 1 for SNLEC (3/20, 15%) was lower than that for NPC (19/36, 52.8%). The expression rates of BZLF1 protein (2/20, 10.0%), diffuse early antigen (19/20, 95.0%), viral capsid antigen (15/20, 75.0%), and membrane antigen (13/20, 65.0%) for SNLEC were higher than those (0/36, 0.0%; 31/36, 86.0%; 18/36, 50%; and 14/36, 38.9%) for NPC. CONCLUSIONS: SNLEC is not uncommon in Guangzhou. This tumour is also consistently associated with EBV infection like NPC. As compared to NPC, the EBV harbored in SNLECs seems to express the EBV nuclear antigen 1 weakly and has a lower expression rate of latent membrane protein 1 as well as higher expression rates of EBV lytic products.

Adult↗

PubMed2001

[The value of number connection test in the diagnosis of subclinical hepatic encephalopathy].

OBJECTIVE: To explore the influencing factors and diagnostic values of number connection test (NCT) in detection of subclinical hepatic encephalopathy (SHE). METHODS: NCT was carried out in four hundred and fifty healthy volunteers to explore the influencing factors and to work out a reference value. Then forty patients with liver cirrhosis were studied with NCT, intelligence quotient (IQ) and evoked potentials(EP) to determine the value of NCT in the diagnosis of SHE. RESULTS: (1) NCT results were influenced by age and educational background. The older the age and the lower the educational level, the longer the NCT time (P < 0.001); (2) The abnormal rate of NCT was 30% (12/40), being lower than the IQ abnormal rate of 58% (23/40) (P < 0.01). (3) IQ or/and EP were abnormal in 85%. (4) The combination of four tests i.e. block design, picture arrangement, object assembly and NCT were abnormal in 53% of the patients. Comparing with the abnormal rate (58%) of full set of IQ test, the sensitivity and specificity were 87% and 94%, respectively. CONCLUSIONS: NCT result was influenced by age and educational background and the sensitivity was low for the scanning of SHE. Combination of four psychometric tests: block design test, picture arrangement, object assembly and NCT was recommended to substitute full set of IQ test in the diagnosis of SHE.

Adult↗

PubMed2001

Treatment of distal femoral nonunion and delayed union by using a retrograde intramedullary interlocking nail.

OBJECTIVE: To analyze the causes of distal femoral nonunion and delayed union and assess the outcome of the corresponding treatment, retrograde intramedullary interlocking nail (RIIN). METHODS: From June 1995 to December 1998, 15 patients (9 males and 6 females) with distal femoral nonunion and delayed union were treated with RIIN. The average age of the patients was 34.5 years (23-46 years). Bone grafting was performed in 10 patients, closed reaming was done in the other 5 patients. Correction osteotomy was performed in 2 patients, and intra-articular release of knee adhesion in 11 patients. X-ray examination and knee society clinical rating system (KSS) were used to evaluate the results. RESULTS: All fractures were followed up for at least 9 months with average follow-up duration of 14.5 months (9-33 months). Solid union was documented in all patients at 6.4 months on average. There were no infections or malunions in this series. Based on the final follow-up data, acceptable functional range of motion (ROM) of over 90 degrees was achieved in most patients. The average ROM was 93.5 degrees with significant improvement of 28 degrees (42.7%, P<0.05) compared with the preoperative ROM. The average knee score was 96. Excellent ROM emerged in 13 patients. The knee function score was 90.5 on average. CONCLUSIONS: The main causes of distal femoral nonunion and delayed union are improper indications and improper use of the implants. RIIN is an effective alternative for treatment of distal femoral nonunion and delayed union because it can provide a stable and reliable fixation which is beneficial for early functional exercise of knee. Bone grafting, closed reaming and intra-articular release of knee adhesion should be considered in order to enhance the bone healing and improve ROM and the knee function.

Adult↗

PubMed2001

[Response of keloid fibroblasts to the effect of tumor necrosis factor-alpha(TNF-alpha)].

OBJECTIVE: To investigate the biologic behavior of keloid fibroblasts and the pathogenesis of keloid. METHODS: Human dermal fibroblasts cultured from normal skin and keloid were treated with tumor necrosis factor-alpha(TNF-alpha) for 48 hours at 10(3) U/ml and 10(4) U/ml. Collagen production by fibroblasts was assessed by 3H-proline in corporation into pepsin-resistant, precipitated extracellular collagenous protein. RESULTS: TNF-alpha caused a concentration-dependent reduction in collagen production in normal dermal fibroblasts. Treatment with TNF-alpha at 10(3) U/ml significantly reduced the collagen synthesis in keloid fibroblasts (P < 0.01). However, the collagen synthesis in keloid fibroblasts did not further decreased after exposure to TNF-alpha at 10(4) U/ml. CONCLUSIONS: Keloid fibroblasts may remain less sensitive to the inhibitory effects of TNF-alpha on collagen synthesis to a certain extent.

Collagen↗

PubMed2001

[Supercritical and near-critical fluid solvents assisted reaction and separation processes].

The tunability of supercritical and near-critical fluid (S/NCF) solvents offers environmental improvements and economic advantages from improved performances and flexibility for separation and reaction processes through density changes or cosolvents. The paper reviews the sustainable reaction and separation processes in S/NCF solvents such as supercritical carbon dioxide and near-critical water.

Acids↗

PubMed2000

Synthesis of C-protected alpha-amino aldehydes of high enantiomeric excess from highly epimerizable N-protected alpha-amino aldehydes.

A new procedure for the preparation of C-protected alpha-amino aldehydes of high enantiomeric excess is illustrated using five differently substituted alpha-(N-Fmoc)amino aldehydes as starting materials. Highly epimerization-prone substrates were converted to the corresponding morpholino nitrile-protected alpha-amino aldehydes with minimal racemization (products >/= 89% ee). Morpholino nitrile derivatives of phenylglycinal were crystallized and subjected to X-ray structural analysis, allowing for definitive determination of the stereochemistry of amino nitrile formation. A rationale for the stereoselectivity of amino nitrile formation is presented.

Aldehydes↗

PubMed2000

IL-2 induces the association of IL-2Rbeta, lyn, and MAP kinase ERK-1 in human neutrophils.

IL-2, first identified as a T cell growth factor, has been proven to activate many cell types including polymorphonuclear neutrophils (PMN3). However, the mechanisms involved in PMN activation, especially the signaling pathways used by the IL-2R, are currently unknown. Here we demonstrate that IL-2 has the ability to induce protein tyrosine kinases in human PMN, and we provide the first evidence that lyn kinase is activated and physically associated with MAP kinase/ERK1. Co-immunoprecipitation experiments with anti-IL-2Rbeta and Western blotting with anti-p53/56lym revealed that lyn protein was present in IL-2R precipitates and that the association of lyn with IL-2Rbeta was markedly elevated by IL-2 stimulation. Furthermore the activity of lyn kinase, evaluated by an in vitro kinase assay with enolase as a substrate, increased following IL-2 stimulation. Another important finding was that, upon IL-2 activation, MAPK/ERK1 was also phosphorylated in PMN. A direct association between lyn and ERK1 was initially demonstrated by co-immunoprecipitation/Western blotting and then definitively proven by the use of a GST-ERK1 fusion protein. We showed that ERK1 binds lyn only in IL-2 stimulated PMN, but not in unstimulated PMN. These results suggest that IL-2 can promote the association of lyn protein tyrosine kinase with IL-2Rbeta as well as the direct binding of MAPK/ERK1 to lyn. The signaling pathway utilized by human PMN in response to IL-2 may thus involve the association of lyn with IL-2Rbeta and the activation process also triggers the recruitment and activation of a specific ERK.

Cells, Cultured↗

PubMed2000

Pivotal role of phosphoinositide-3 kinase in regulation of cytotoxicity in natural killer cells.

The mitogen-activated protein kinase-extracellular signal-regulated kinase signaling element (MAPK-ERK) plays a critical role in natural killer (NK) cell lysis of tumor cells, but its upstream effectors were previously unknown. We show that inhibition of phosphoinositide-3 kinase (PI3K) in NK cells blocks p21-activated kinase 1 (PAK1), MAPK kinase (MEK) and ERK activation by target cell ligation, interferes with perforin and granzyme B movement toward target cells and suppresses NK cytotoxicity. Dominant-negative N17Rac1 and PAK1 mimic the suppressive effects of PI3K inhibitors, whereas constitutively active V12Rac1 has the opposite effect. V12Rac1 restores the activity of downstream effectors and lytic function in LY294002- or wortmannin-treated, but not PD98059-treated, NK cells. These results document a specific PI3K-->Rac1-->PAK1-->MEK-->ERK pathway in NK cells that effects lysis.

Cell Line↗

PubMed2000

Retinoblastoma protein activation of interleukin 8 expression inhibits tumor cell survival in nude mice.

Loss of retinoblastoma protein (Rb) has been implicated in the formation of a variety of human malignancies. Restoration of Rb expression in the cell lines representing these tumors eliminates or significantly reduces tumorigenicity in nude mice, but the mechanism for this Rb effect is unknown. Results from this study indicated that Rb expression reduced tumor cell survival in nude mice by dramatically enhancing interleukin 8 (IL-8) secretion. IL-8 secreted by the Rb-transformed cells attracted neutrophils in vitro and tumor-infiltrating neutrophils in vivo, which is consistent with the Rb-mediated tumor regression being dependent on IL-8. The apparent, contradictory roles of IL-8 as a protumorigenic and antitumorigenic cytokine are discussed.

Animals↗

PubMed2000

[Repairing peripheral nerve defects by tissue engineering techniques:an experimental study].

OBJECTIVE: To develop a novel effective substitute material or technique to repair peripheral nerve gap. METHODS: We inoculated expanded Schwann cells (SCs) at re-arranged bio-absorbable polymer polyglycolic acid (PGA) fiber and incubated for two weeks, then we developed a novel tissue-engineered scaffolds. The scaffolds were used as cellular isografts to bridge 15 mm long gap of sciatic nerve in inbred strains of Wistar rats. In an autologous and pure PGA fiber control group, the same surgical procedure was used. Evaluation included general observation, electromyographic examination, muscle measurement, and histological observation of serial sections at 12 weeks after surgery. The total number and density of reinnervation and thickness of myelin sheath was measured by computerized image analysis. RESULTS: SCs put out a long and thin prominence and migrated along the PGA fibers in spirality or parallel when they divided and finally rank into a cell-chain formation similar to Büngner's band. TEM/SEM and immunohistochemical survey demonstrated that the SCs at PGA fiber also secreted a great deal of ECMs included laminin, which play a very important role in peripheral nerve regeneration. Non-tubular scaffold comprised SCs and laminin (LN) channel in three-dimensional longitudinal rank. Animal transplantation study indicated the sensory and motor functional results of hindlimbs of experimental group rats reached to similar level of those found in nerve autograft control group. The number of reinnervation in the experimental group rats was slightly fewer than that in nerve autograft control group; but the axonal density was just reversal between the two groups because of a large area ischemic necrosis in the center of nerve autografts. CONCLUSION: This new paradigm offers a potential solution to repairing a long gap of peripheral nerve.

Animals↗

PubMed1999

Unmodified supported thiol/lipid bilayers: studies of structural disorder and conducting mechanism by cyclic voltammetry and AC impedance.

Supported thiol/lipid bilayer assembly, one of the most spectacular bilayer systems in recent years, has provided a good model to study biomembranes because of its high mechanical stability. In this work, the structural and conducting property of unmodified Au supported octadecanethiol/phosphatidylcholine bilayers were investigated using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The forming process of bilayer was monitored by capacitance plane plot. The normalized membrane capacitance of supported bilayer is 0.52 microF cm(-2). Kinetically controlled voltammograms determined by Butler-Volmer equation were obtained for both thiol monolayer and thiol/lipid bilayer in linear sweep voltammetry. Results of EIS experiment indicate that collapsed sites and pinhole defects exist in thiol monolayer and lipid monolayer, respectively. The difference between the values of experimental and theoretical standard electron transfer rate constant indicates that the conducting mechanism of Au supported thiol monolayer is electron tunneling at collapsed sites. The conducting mechanism of Au supported thiol/lipid bilayer is attributed as the following: the electroactive species could diffuse through pinholes in the lipid monolayer and reach collapsed sites in thiol monolayer, where electron transfer occurs via a tunneling process. The fractional coverage of the lipid monolayer measure by EIS experiments is about 0.98 or higher.

Electrochemistry↗

PubMed1998

Syntheses of amino nitrones. Potential intramolecular traps for radical intermediates in monoamine oxidase-catalyzed reactions.

Monoamine oxidase (MAO) is a flavin-dependent enzyme that catalyzes the oxidative deamination of a variety of amine neurotransmitters and toxic amines. Although there have been several studies that support the intermediacy of an amine radical cation and an alpha-radical during enzyme catalysis, there is no direct, i.e. EPR, evidence for these species as they are formed. Amino nitrones have been designed which, upon radical formation would produce an intermediate that is a resonance structure of the corresponding nitroxyl radical, which should be observable by EPR spectroscopy. Syntheses of seven different amino nitrones, three acyclic, and four cyclic analogues were attempted. The protected amino nitrones were stable, but all three of the acyclic amino nitrones were unstable. One of the cyclic analogues was very stable (39), one was stable only in organic solvents (40), one was stable only in aqueous medium below pH 6.5 (41), and the other (42) was stable for just a short time at room temperature, decomposing to a stable free radical. None of these analogues produced a MAO-catalyzed radical, yet 41 is a poor substrate (Km=0.2mM; k(cat) = 0.034 min-1) and 39 is a mixed inhibitor (Ki = 26.5 mM). Although this approach does not appear to be applicable to amino nitrones, it should be a valuable approach for other enzymes where radical intermediates are suspected and nonamine nitrones can be utilized.

Amines↗

PubMed1998

The P2 protein of rice dwarf phytoreovirus is required for adsorption of the virus to cells of the insect vector.

Intact particles of rice dwarf phytoreovirus adsorbed to and entered monolayer-cultured cells of the insect vector Nephotettix cincticeps and multiplied within the cells. Particles that lacked the P2 protein neither attached to nor infected such cells. Furthermore, P2-free particles obtained from a transmission-competent isolate of the virus were unable to infect insect vectors that had been allowed to feed on these virus particles through a membrane. However, when such virus particles were injected into insects via a glass capillary tube they successfully infected the insects, which became able to transmit the virus. These results support the hypothesis that, while P2-free particles can neither interact with nor infect cells in the intestinal tract of the insect vector, they do retain the ability to infect such cells when physically introduced into the hemolymph by injection.

Adsorption↗