PubMed Health⌕ Search

Biomedical subjects

Jun Zhou

Publications and source records attributed to Jun Zhou.

At least 37 records · Page 2Linked to original sources
PubMed2006

CD147, MMP-2, MMP-9 and MVD-CD34 are significant predictors of recurrence after liver transplantation in hepatocellular carcinoma patients.

OBJECTIVE: The prognostic role of tumor biological markers (biomarkers) in predicting recurrence of hepatocellular carcinoma (HCC) was investigated in this study, the results of which may help to select appropriate candidates for liver transplantation (LT). METHODS: Tissue samples from 82 HCC patients with cirrhosis who had undergone LT were immunohistochemically stained with antibodies of anti-CD147, anti-matrix metalloproteinases-2 (MMP-2), MMP-9 and anti-vascular endothelial growth factor (VEGF). Tumor microvessel density (MVD) was evaluated by using CD34. Multivariate Cox regression analysis was performed to identify the relevant prognostic factors. RESULTS: A significant correlation was found between the expression of CD147, VEGF, MMP-2, MMP-9 and MVD-CD34 in HCC. Tumor CD147 expression (P < 0.0001), tumor MVD-CD34 (P < 0.0001), MMP-9 in stromal compartment (P = 0.0257) and tumor VEGF expression (P = 0.0335) were significantly associated with the recurrence in HCC patients after LT. Univariate analysis showed that strong CD147 expression and high MVD-CD34 were significantly associated with poor tumor recurrence-free survival after LT (P < 0.0001). Multivariate analysis indicated that CD147 (P = 0.0001), MVD-CD34 (P = 0.0118), MMP-2 (P = 0.0312) and MMP-9 (P = 0.0280) in stromal compartment were all significant predictors in predicting HCC recurrence, while VEGF, MMP-2 and MMP-9 in tumor compartment were not significantly associated with poor prognosis. CONCLUSIONS: The tumor biomarkers CD147 and MVD-CD34 are more feasible markers for rational selection of LT candidates with HCC. MMP-9 and MMP-2 expression in stromal compartment, combined with pTNM tumor grade, may be helpful in predicting poor prognosis in HCC patients after LT.

Adult↗
PubMed2006

A new triterpene and anti-hepatitis B virus active compounds from Alisma orientalis.

A new triterpenoid named alisol O ( 1) was isolated from the rhizomes of Alisma orientalis, together with six known compounds: alisol A 24-acetate ( 2), 25-anhydroalisol A ( 3), 13 beta,17 beta-epoxyalisol A ( 4), alisol B 23-acetate ( 5), alisol F ( 6), and alisol F 24-acetate ( 7). Based on 1D and 2D-NMR data (HMQC, HMBC, COSY, ROESY), the structure of the new compound was deduced to be 11-dehydroxy-12-dehydroalisol F-24-acetate ( 1). Compounds 2 - 7 exhibited inhibitory activity in vitro on hepatitis B virus (HBV) surface antigen (HBsAg) secretion of the Hep G2.2.15 cell line with IC (50) values of 2.3, 11.0, 15.4, 14.3, 0.6 and 7.7 microM, and on HBV e antigen (HBeAg) secretion with IC (50) values of 498.1, 17.6, 41.0, 19.9, 8.5 and 5.1 microM, respectively.

Alisma↗
PubMed2006

Kinetic studies of adsorption of Pb(II), Cr(III) and Cu(II) from aqueous solution by sawdust and modified peanut husk.

Sawdust and modified peanut husk were used as adsorbents to remove Pb(II), Cr(III) and Cu(II) from aqueous solution. Results of kinetic experiments demonstrated that the adsorption was effective and rapid. Three different kinds of kinetic models (i.e., intraparticular diffusion model, Lagergren-first-order and second-order equations) were used to investigate the adsorption mechanisms. The adsorption of heavy metals on sawdust and modified peanut husk is not an intraparticular diffusion control. The kinetic adsorption data can be described by the second-order equation and the adsorption might be a rate-limiting control. The suitability of the adsorbent was tested by fitting the adsorption data with Langmuir and Freundlich isotherms, which gave good fits with both isotherms.

Adsorption↗
PubMed2006

Structure-activity relationships of triazolopyridine oxazole p38 inhibitors: identification of candidates for clinical development.

The synthesis, structure-activity relationship, in vivo activity, and metabolic profile for a series of triazolopyridine-oxazole based p38 inhibitors are described. The deficiencies of the lead structure in the series, CP-808844, were overcome by changes to the C4 aryl group and the triazole side-chain culminating in the identification of several potential clinical candidates.

Chemistry, Pharmaceutical↗
PubMed2006

Dimerization-induced corepressor binding and relaxed DNA-binding specificity are critical for PML/RARA-induced immortalization.

The pathogenesis of acute promyelocytic leukemia involves the transcriptional repression of master genes of myeloid differentiation by the promyelocytic leukemia-retinoic acid receptor alpha (PML/RARA) oncogene. PML-enforced RARA homodimerization allows the tighter binding of corepressors, silencing RARA target genes. In addition, homodimerization dramatically extends the spectrum of DNA-binding sites of the fusion protein compared with those of normal RARA. Yet, any contribution of these two properties of PML/RARA to differentiation arrest and immortalization of primary mouse hematopoietic progenitors was unknown. We demonstrate that dimerization-induced silencing mediator of retinoid and thyroid receptors (SMRT)-enhanced binding and relaxed DNA-binding site specificity are both required for efficient immortalization. Thus, enforced RARA dimerization is critical not only for triggering transcriptional repression but also for extending the repertoire of target genes. Our studies exemplify how dimerization-induced gain of functions converts an unessential transcription factor into a dominant oncogenic protein.

Animals↗
PubMed2006

Growth of large-area aligned molybdenum nanowires by high temperature chemical vapor deposition: synthesis, growth mechanism, and device application.

Large-area aligned Mo nanowires have been grown on stainless steel substrates by high-temperature chemical vapor deposition with the use of Mo metal. The detailed physical and chemical growth processes regarding the formation of the nanowires have been investigated using mass spectroscopy, thermogravimetry, and differential scanning calorimetry analysis, as well as structure analysis by electron microscopy. In reference to Gibbs energy calculation, our study reveals that the growth relies on the decomposition of MoO2 vapors through condensation of its vapor at high substrate temperatures. The aligned growth is a result of competing growth with the nanowires normal to the substrate surface reaching the final growth front. The field emission measurement and the vacuum luminescent tube study show that the Mo nanowires have potential application as electron emitters.

Journal Article↗
PubMed2006

Electrical alternans and hemodynamics in the anesthetized guinea pig can discriminate the cardiac safety of antidepressants.

INTRODUCTION: The arrhythmogenic risk of fluoxetine, citalopram, and venlafaxine were evaluated through preclinical assays measuring hERG, blood pressure and electrical alternans over their respective clinical unbound concentration ranges. METHODS: Anesthetized guinea pigs were instrumented with jugular and carotid cannulae for drug infusion and blood pressure monitoring respectively; a thoracotomy was performed for placement of a monophasic action potential probe on the left ventricle and for placement of pacing wires on the left ventricular apex. Drugs were infused as a 5-min loading dose immediately followed by a 10-min maintenance dose to achieve clinically relevant plasma concentrations; blood samples were taken at the end of each maintenance dose. Ventricular pacing was performed twice at baseline and at each dose level as follows: 50 preconditioning-beats at S1=220 (or 240) ms immediately followed by 30 test-beats at S2=200 ms. This S1-S2 protocol was repeated for S2=190 to 140 ms. HERG and calcium current measurements were recorded in HEK-293 cells stably expressing hERG potassium currents and freshly isolated guinea pig cardiac myocytes using the whole-cell configuration of the patch clamp technique. RESULTS: Physiologically relevant inhibition (IC(20)) of hERG occurred at concentrations 22-fold (fluoxetine), 9-fold (citalopram), and 11-fold (venlafaxine) beyond their respective clinically effective concentration (C(eff)). At the highest achievable levels, fluoxetine (20-fold C(eff)) and citalopram (28-fold C(eff)) significantly decreased heart rate and/or blood pressure as well as increasing electrical alternans by 5 and 18 ms respectively. Venlafaxine increased blood pressure at only 1.3-fold C(eff), but did not increase electrical alternans at the highest achievable dose (3.1-fold C(eff)). DISCUSSION: These data suggest that evaluating other dose limiting side effects in relation to a drug's therapeutic range may be crucial for accurate assessment of arrhythmia liability.

Action Potentials↗
PubMed2006

Inhibition of the mitotic kinesin Eg5 up-regulates Hsp70 through the phosphatidylinositol 3-kinase/Akt pathway in multiple myeloma cells.

The microtubule-dependent motor protein Eg5 plays a critical role in spindle assembly and maintenance in mitosis. Herein we show that the suppression of Eg5 by a specific inhibitor arrested mitosis, induced apoptosis, and up-regulated Hsp70 in human multiple myeloma cells. Mechanistically, Hsp70 induction occurred at the transcriptional level via a cis-regulatory DNA element in Hsp70 promoter and was mediated by the phosphatidylinositol 3-kinase/Akt pathway. Eg5 inhibitor-mediated Hsp70 up-regulation is cytoprotective because blocking Hsp70 induction directly by antisense or small interfering RNA or indirectly by inhibiting the phosphatidylinositol 3-kinase/Akt pathway significantly increased Eg5 inhibitor-induced apoptosis. Furthermore, a farnesyltransferase inhibitor interacted synergistically with the Eg5 inhibitor in inducing apoptosis through disrupting the Akt/Hsp70 signaling axis. These findings provide the first evidence for Eg5 inhibitor activity in hematologic malignancy and identify Hsp70 up-regulation as a critical mechanism responsible for modulating myeloma cell sensitivity to Eg5 inhibitors. In addition, these findings suggest that a combination of Eg5 inhibitors with agents abrogating Hsp70 induction would be useful for myeloma therapy in the clinic.

Apoptosis↗
PubMed2006

Rational design of the microtubule-targeting anti-breast cancer drug EM015.

We studied in silico docking of noscapine onto tubulin, combined with calculations of surface charge, pi-pi, van der Waals, and hydrogen bonding interactions, to rationally design a new compound, EM015. This tubulin-binding semisynthetic compound is a selective and potent anti-breast cancer agent and displays a 20-fold lower IC(50) against many tumor cells compared with our founding compound, (S)-6,7-dimethoxy-3-((R)-4-methoxy-6-methyl-5,6,7,8-tetrahydro[1,3]-dioxolo-[4,5-g]isoquinolin-5-yl)isobenzo-furan-1(3H)-one (noscapine). Furthermore, EM015 is also effective against a variety of drug-resistant cells. Surprisingly, the cell cycle profile of nontumorigenic normal cells is not affected. Many antimicrotubule cancer drugs in clinic today, particularly taxanes and Vincas, face challenges including frequent visits to the hospital for prolonged i.v. infusions, toxicities, and tumor recurrences due to drug resistance. EM015, on the other hand, is orally available, regresses breast tumor xenografts in nude mice models, and increases longevity. Furthermore, we have failed to observe any detectable toxicity in tissues, such as liver, kidney, spleen, lung, heart, and brain, as well as neurons, which are common targets of antimicrotubule drug therapy. Thus, EM015 has a great promise in the clinic.

Animals↗
PubMed2006

Two novel non-viral gene delivery vectors: low molecular weight polyethylenimine cross-linked by (2-hydroxypropyl)-beta-cyclodextrin or (2-hydroxypropyl)-gamma-cyclodextrin.

Two novel polymers of low molecular weight polyethylenimine cross-linked by (2-hydroxypropyl)-beta-cyclodextrin or (2-hydroxypropyl)-gamma-cyclodextrin showed lower cytotoxicity and higher transfection efficiency for the delivery of plasmid DNA compared with those of polyethylenimine (PEI, 25 kDa).

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed2006

Use of arterially perfused rabbit ventricular wedge in predicting arrhythmogenic potentials of drugs.

INTRODUCTION: A growing number of drugs have reportedly been associated with delayed ventricular repolarization and a potentially fatal but rare arrhythmia, torsade de pointes (TdP). There is obviously a call for a validated proarrhythmia model that distinguishes proarrhythmic drugs from nonarrhythmogenic drugs. METHODS: In this article, we validated the arterially perfused rabbit left ventricular wedge preparation model and examined its use in predicting proarrhythmic potentials of drugs. A fairly detailed methodological description about this technically challenging model was given, aiming to help others establish the assay successfully. Parameters commonly used in the action potential studies were verified and critical experimental conditions (e.g. stability and reproducibility of recordings) were examined. Six commercially available compounds with various proarrhythmic potentials were administered in the model to evaluate their correlations with individual clinical outcomes. RESULTS: Our study indicated that, in a successful experiment, the action potential duration (APD) can be stably maintained for several hours without intervention. Dofetilide, DL-sotalol, cisapride, risperidone and moxifloxacin increased endo- and epicardial APD(90), QT interval and T(P-E) (peak-to-end time of the T wave) in a reverse use-dependent manner within clinically relevant concentration ranges. Phase 2 early afterdepolarizations (EADs) were observed at 1.6, 2.3, 16.7, 37.5 and 7.9 fold, respectively, their corresponding unbound therapeutic concentrations. In contrast, fluoxetine at up to 3 microM (approximately 35 fold unbound therapeutic mean plasma concentration after 60 mg/day, p.o. for 5 weeks) had only a mild prolonging effect on APD(90) and QT with essentially no effect on T(P-E). DISCUSSION: Our results strongly support the usefulness of this model in predicting a compound's arrhythmogenic potential in humans within clinically relevant concentration ranges, and the experimental results with this model need to be interpreted in light of each drug's pharmacokinetic and pharmacodynamic behavior in clinic.

Action Potentials↗
PubMed2006

Safety evaluation of protein of silkworm (Antheraea pernyi) pupae.

The protein of silkworm pupae (PSP) has been thought to be a new available source of high quality protein that contains all the amino acids needed by the human body. The safety of PSP was evaluated systematically by a series of acute and sub-acute toxicological tests: (i) Acute toxicity test: The oral maximum tolerated dose of PSP was more than 15.0 g/kg body weight in mice, due to the absence of toxicity according to the criteria of acute toxic classifications; (ii) Mutagenicity test: PSP had no mutagenicity, as judged by a negative Ames test, mouse bone marrow cell micronucleus test and mouse sperm abnormality test; (iii) 30 days feeding study: No deaths or abnormal hematological, clinical chemical and histopathological changes and clinical signs had been found in rats when administrated PSP at 0.30, 0.75 and 1.50 g/kg/day to the rats for 30 days in each group during the test, respectively. No statistically significant differences had been found in body weights, food consumption and food efficiency of rats in each test group (P>0.05). These results indicate that PSP can be generally regarded as safe at a maximum dose of 1.50 g/kg/day in rats.

Animals↗
PubMed2006

CD147 overexpression on synoviocytes in rheumatoid arthritis enhances matrix metalloproteinase production and invasiveness of synoviocytes.

Macrophage-like synoviocytes and fibroblast-like synoviocytes (FLS) are known as the most active cells of rheumatoid arthritis (RA) and are close to the articular cartilage in a position enabling them to invade the cartilage. Macrophage-like synoviocytes and FLS expression of matrix metalloproteinases (MMPs) and their interaction has aroused great interest. The present article studied the expression of CD147, also called extracellular matrix metalloproteinase inducer, on monocytes/macrophages and FLS from RA patients and its potential role in enhancing MMPs and the invasiveness of synoviocytes. Expression of CD147 on FLS derived from RA patients and from osteoarthritis patients, and expression of CD147 on monocytes/macrophages from rheumatic synovial fluid and healthy peripheral blood were analyzed by flow cytometry. The levels of CD147, MMP-2 and MMP-9 mRNA in FLS were detected by RT-PCR. The role of CD147 in MMP production and the cells' invasiveness in vitro were studied by the co-culture of FLS with the human THP-1 cell line or monocytes/macrophages, by gel zymography and by invasion assay. The results showed that the expression of CD147 was higher on RA FLS than on osteoarthritis FLS and was higher on monocytes/macrophages from rheumatic synovial fluid than on monocytes/macrophages from healthy peripheral blood. RT-PCR showed that the expressions of CD147, MMP-2 and MMP-9 mRNA was higher in RA FLS than in osteoarthritis FLS. A significantly elevated secretion and activation of MMP-2 and MMP-9 were observed in RA FLS co-cultured with differentiated THP-1 cells or RA synovial monocytes/macrophages, compared with those co-cultured with undifferentiated THP-1 cells or healthy control peripheral blood monocytes. Invasion assays showed an increased number of invading cells in the co-cultured RA FLS with differentiated THP-1 cells or RA synovial monocytes/macrophages. CD147 antagonistic peptide inhibited the MMP production and the invasive potential. Our studies demonstrated that the CD147 overexpression on monocytes/macrophages and FLS in RA patients may be responsible for the enhanced MMP secretion and activation and for the invasiveness of synoviocytes. These findings suggest that CD147 may be one of the important factors in progressive joint destruction of RA and that CD147 may be a potential therapeutic target in RA treatment.

Adult↗
PubMed2006

Growth of columnar hydrogel colloidal crystals in water-organic solvent mixture.

A novel emulsion method has been demonstrated to grow columnar hydrogel colloidal crystals by mixing an aqueous suspension of poly-N-isopropylacrylamide-co-allylamine microgels with organic solvent, driven by the coalescence of micelles consisting of organic oil droplets coated by many microgels. This method leads to microgel colloidal crystals of several centimeters growing from the top to the bottom along the gravity direction. Both temperature and polymer concentration play critical roles for the formation of columnar crystals. A phase diagram has been determined, and it can be used as a guide to selectively grow different crystals, including columnar crystals and randomly oriented crystals, and enable the coexistence of columnar crystals and randomly oriented crystals.

Journal Article↗
PubMed2006

Reversal of P-glycoprotein-mediated multidrug resistance in cancer cells by the c-Jun NH2-terminal kinase.

A significant impediment to the success of cancer chemotherapy is multidrug resistance (MDR). A typical form of MDR is attributable to the overexpression of membrane transport proteins, such as P-glycoprotein, resulting in an increased drug efflux. In this study, we show that adenovirus-mediated enhancement of the c-Jun NH2-terminal kinase (JNK) reduces the level of P-glycoprotein in a dose- and time-dependent manner. Protein turnover assay shows that the decrease of P-glycoprotein is independent of its protein stability. Instead, this occurs primarily at the mRNA level, as revealed by reverse transcription-PCR analysis. We find that P-glycoprotein down-regulation requires the catalytic activity of JNK and is mediated by the c-Jun transcription factor, as either pharmacologic inhibition of JNK activity or dominant-negative suppression of c-Jun remarkably abolishes the ability of JNK to down-regulate P-glycoprotein. In addition, electrophoretic mobility shift assay reveals that adenoviral JNK increases the activator protein binding activity of the mdr1 gene in the MDR cells. We further show that the decrease of P-glycoprotein level is associated with a significant increase in intracellular drug accumulation and dramatically enhances the sensitivity of MDR cancer cells to chemotherapeutic agents. Our study provides the first direct evidence that enhancement of the JNK pathway down-regulates P-glycoprotein and reverses P-glycoprotein-mediated MDR in cancer cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Production of epsilon-poly-L-lysine by newly isolated Kitasatospora sp. PL6-3.

A novel epsilon-poly-L-lysine (epsilon-PL)-producing strain PL6-3 was isolated from soil, and was identified as a strain of Kitasatospora sp. This is the first detailed report of production of epsilon-PL by a strain in the genera of Kitasatospora. By controlling the culture pH at 4.0, the yield of epsilon-PL from PL6-3 reached 13.9 g/L after 120 h of cultivation in fed-batch fermentation. The morphological characteristics of Kitasatospora sp. PL6-3 in culture broth were different from those reported from strains of Streptomycetaceae, as no mycelium pellets were observed during the course of fermentation of PL6-3, which was beneficial to the assimilation of nutrition and secretion of the products. Furthermore, the molecular mass of the purified epsilon-PL from PL6-3 was determined to be 5.01 kDa by SDS-PAGE and 5.05 kDa by gel permeation chromatography, indicating that the epsilon-PL produced by this strain might be composed of 40 lysine residues. Usually, epsilon-PL with more lysine residues showed higher antimicrobial activity; however, it was difficult to obtain epsilon-PL with more than 36 lysine residues in this study. As a result, epsilon-PL from Kitasatospora sp. PL6-3, which contains more lysine residues than that from other strains, is more promising in the field of food preservatives.

Polylysine↗
PubMed2006

Proteome analysis of sorbitol fermentation specific protein in Vibrio cholerae by 2-DE and MS.

Vibrio cholerae can be differentiated into epidemic and non-epidemic strains by sorbitol fermentation speed, but little research has been done on its mechanisms. In this study, we investigated differential protein expression of the two strains in response to sorbitol metabolism. V. cholerae strains were cultured in media with and without sorbitol, respectively. Proteins were separated by 2-DE, and those that showed different expression in the two media were identified by MALDI-TOF MS. Fifteen proteins in epidemic strains and 11 proteins in non-epidemic strains showed a different expression in sorbitol medium. Among them, 4 proteins were common to epidemic and non-epidemic strains. Gene sequence analysis showed that some mutations occurred in these proteins between the two strains. Potential functions of these proteins included sugar uptake, amino acid uptake, electron transport, sulfate and thiosulfate transport.

Amino Acid Sequence↗