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Jun Wang

Publications and source records attributed to Jun Wang.

At least 55 records · Page 3Linked to original sources
PubMed2006

Inhibitory effects of a specific phage-displayed peptide on high peritoneal metastasis of gastric cancer.

Peritoneal dissemination in gastric cancer is the most frequent cause of the noncurative resection and recurrence after curative resection. We, therefore, evaluated the feasibility of a peptide, which was obtained by screening a random phage display library, in the treatment of peritoneal metastases of gastric cancer. In this study, a novel cell line, GC9811-P, with a high potential peritoneal metastasis of gastric cancer derived from its parental cell line, GC9811, was established. Using a phage display library, we isolated a specific peptide that selectively bound to GC9811-P cells rather than its parental GC9811cells. The isolated phage-displaying peptide, SMSIASPYIALE (named peptide PIII), was obtained after four rounds of selection, showing a tendency to preferentially bind to GC9811-P cells compared with a panel of other gastric cancer cell lines, and preferentially accumulate in peritoneal metastasis tumor tissue in comparison with control organs, peritoneum, liver, pancreas, spleen, lung, and kidney. Further study showed that synthetic peptide PIII could significantly inhibit adhesive and invasional ability of GC9811-P cells and could effectively block the corresponding phage binding to the GC9811-P cells, whereas, exposure of the cells to various concentrations of peptide PIII showed no obvious cell growth inhibition. Furthermore, a highly reproducible animal experimental model of gastric cancer with peritoneal dissemination was established in nude mice by injecting a suspension of the cell line into the gastric wall of nude mice. Animals intraperitoneally treated with peptide PIII in this model or another animal model of gastric cancer with peritoneal dissemination established using MKN45 cells showed suppressed tumor metastasis to peritoneum and significantly prolonged survival. In conclusion, the selected peptide PIII was a biologically active peptide and could effectively inhibit peritoneal dissemination of gastric cancer.

Animals↗
PubMed2006

Differential pattern of inflammatory molecule regulation in intestinal epithelial cells stimulated with IL-1.

To better predict the consequences of blocking signal transduction pathways as a means of controlling intestinal inflammation, we are characterizing the pathways up-regulated by IL-1 in intestinal epithelial cells (IEC). IL-1beta induced increased mRNA levels of MIP-2, MCP-1, RANTES, inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2) in the IEC-18 cell line. IL-1beta activated NF-kappaB but not ERK or p38. Infecting cells with adenovirus expressing a mutated gene for IkappaBalpha (IkappaBAA) blocked IL-1-induced mRNA increases in MIP-2, MCP-1, and iNOS but not COX-2 or RANTES. Expression of IkappaBAA attenuated the IL-1-induced increase in COX-2 protein. Unexpectedly, RANTES mRNA increased, and protein was secreted by cells expressing IkappaBAA in the absence of IL-1. Adenovirus-expressing IkappaBAA, blocking protein synthesis, and IL-1beta all resulted in activation of JNK. The JNK inhibitor SP600125 prevented the RANTES increases by all three stimuli. A human enterocyte line was similarly examined, and both NF-kappaB and JNK regulate IL-1-induced RANTES secretion. We conclude that in IEC-18, IL-1beta-induced increases in mRNA for MIP-2, MCP-1, and iNOS are NF-kappaB-dependent, whereas regulation of RANTES mRNA is independent of NF-kappaB but is positively regulated by JNK. IL-1beta-induced mRNA increases in COX-2 mRNA are both NF-kappaB- and MAPK-independent but the translation of COX-2 protein is NF-kappaB-dependent. This pattern of signaling due to a single stimulus exposed the complexities of regulating inflammatory genes in IEC.

Cell Line↗
PubMed2006

Global exponential stability of recurrent neural networks with time-varying delays in the presence of strong external stimuli.

This paper presents new theoretical results on the global exponential stability of recurrent neural networks with bounded activation functions and bounded time-varying delays in the presence of strong external stimuli. It is shown that the Cohen-Grossberg neural network is globally exponentially stable, if the absolute value of the input vector exceeds a criterion. As special cases, the Hopfield neural network and the cellular neural network are examined in detail. In addition, it is shown that criteria herein, if partially satisfied, can still be used in combination with existing stability conditions. Simulation results are also discussed in two illustrative examples.

Animals↗
PubMed2006

Intramuscular immunization with a monogenic plasmid DNA tuberculosis vaccine: Enhanced immunogenicity by electroporation and co-expression of GM-CSF transgene.

Plasmid DNA vaccine has been widely explored for tuberculosis immunization but there is a need to develop the ways to improve its immunogenicity. In this study, we have constructed a plasmid DNA vaccine coding for Ag85A alone or for both Ag85A and GM-CSF and investigated the immune adjuvant effects of electroporation and GM-CSF co-expression, alone or in combination, on CD4 and CD8 T cell IFN-gamma responses, CTL activities and immune protection from pulmonary Mycobacterium tuberculosis challenge in a Balb/c mouse model. We have found that use of electroporation allows a single intramuscular (i.m.) DNA injection to be as effective as repeated i.m. DNA injections in activation of both Ag85A-specific CD4 and CD8 T cells. Co-expression of immune-enhancing cytokine GM-CSF by the same plasmid DNA TB vaccine could further enhance T cell activation including CTL activities on top of electroporation. With regard to immune protection from pulmonary M. tb challenge, use of electroporation also allows a single i.m. DNA injection to be as effective as repeated i.m. DNA injections. Co-expression of GM-CSF transgene also moderately enhances immune protection and such effect is more evident for systemic protection. However, GM-CSF expression has little added effect on immune protection by electroporation-aided immunization protocols. Our findings thus will help with the development of future DNA TB immunization strategies.

Adjuvants, Immunologic↗
PubMed2006

[Effectiveness of backward walking treadmill training in lower extremity function after stroke].

OBJECTIVE: To examine the effectiveness of backward walking treadmill training for restoration of motor function, balance and walking speed in patients with stroke. METHODS: Twenty-six patients with stroke, 17 males and 9 females, aged 36 - 64, with the lower extremity Brunnstrom motor recovery stage at 3 or 4, able to walk for 10 m without walking aid or orthosis, were randomly divided into two equal groups: The patients in the control group were to participate in a 60-minutes conventional training five times a week for three weeks, and the patients in the experimental group received 30-minute conventional training and then 30-minute backward walking training five times a week for three weeks. Before the training and 3 weeks after the training, Fugl-Meyer assessment was used to assess the motor function of the lower extremity (FMA-L), Berg balance scale (BBS) was used to assess the balance function, and 10 m maximum walking speed was measured. RESULTS: After the three-week training period, the FMA-L score of the experimental group was 28.0 +/- 3.3, significantly higher than that of the control group (25.5 +/- 2.3, P = 0.033); the BBS score of the experimental group was 51.4 +/- 1.8, significantly higher than that of the control group (47.3 +/- 3.7, P = 0.001, and 10 m MWS of the experimental group was 57 +/- 17, significantly higher than that of the control group (43 +/- 16, P = 0.034). CONCLUSION: A safe and feasible intervention, additional backward walking therapy helps improve the damaged motor function, balance, and walking speed of the patients with stroke.

Exercise Test↗
PubMed2006

Fluorescence study of DNA binding and bending by EcoRI DNA methyltransferase.

We have applied fluorescence anisotropy and fluorescence resonance energy transfer (FRET) techniques to study the interaction between EcoRI DNA methyltransferase (M.EcoRI) and its target DNA in solution. Upon binding with M.EcoRI, the dsDNA containing GAATTC bends to flip out the second adenine for methylation. The binding affinity of M.EcoRI to two dsDNA fragments (20 and 38 bp) was studied with fluorescence anisotropy. Their binding constants at different temperatures from 20 to 40 degrees C were obtained, and the thermodynamic parameters of binding were derived. The results showed that M.EcoRI had a higher binding affinity to the short dsDNA strand than to the long one, and its binding to DNA was primarily entropy-driven. By labeling the 5' ends of the 20-bp dsDNA with two fluorescent dyes, fluorescein (FAM) and tetramethylrhodamine (TMR), we were able to monitor the enhanced TMR fluorescence in the presence of M.EcoRI. The end-to-end distance of the dsDNA determined from the FRET efficiency was changed from 72.4 to 63.4 A, and the DNA bending angle was estimated as 57.8 degrees .

Adenine↗
PubMed2006

Sensitive immunoassay of a biomarker tumor necrosis factor-alpha based on poly(guanine)-functionalized silica nanoparticle label.

A novel electrochemical immunosensor for the detection of tumor necrosis factor-alpha (TNF-alpha) based on poly(guanine)-functionalized silica nanoparticles (NPs) label is presented. The detection of mouse TNF-alpha via immunological reaction is based on a dual signal amplification: (1) a large amount of guanine residues introduced on the electrode surface through sandwich immunoreaction and poly(guanine)-functionalized silica NP label; (2) Ru(bpy)3(2+)-induced catalytic oxidation of guanine, which results in great enhancement of anodic current. The synthesized silica NP conjugates were characterized with atomic force microscopy, X-ray photoelectron spectroscopy, and electrochemistry. These experiments confirmed that poly(guanine) and avidin were immobilized on the surface of silica NPs. The performance of the electrochemical immunosensor was evaluated and some experiment parameters (e.g., concentration of Ru(bpy)3(2+), incubation time of TNF-alpha, etc.) were optimized. The detection limit for TNF-alpha is found to be 5.0 x 10(-11) g mL(-1) (2.0 pM), which corresponds to 60 amol of TNF-alpha in 30 microL of sample. This immunosensor based on the poly(guanine)-functionalized silica NP label offers great promise for rapid, simple, cost-effective analysis of biological samples.

Animals↗
PubMed2006

Electrochemical proteolytic beacon for detection of matrix metalloproteinase activities.

This communication describes a novel method for detecting matrix metalloproteinase-7 activity using a peptide substrate labeled with a ferrocene reporter. The substrate serves as a selective "electrochemical proteolytic beacon" (EPB) for this metalloproteinase. The EPB is immobilized on a gold electrode surface to enable "on-off" electrochemical signaling capability for uncleaved and cleaved events. The EPB is efficiently and selectively cleaved by MMP-7 as measured by the rate of decrease in redox current of ferrocene. Direct transduction of a signal corresponding to peptide cleavage events into an electronic signal thus provides a simple, sensitive route for detecting the MMP activity. The new method allows for identification of the activity of MMP-7 in concentrations as low as 3.4 pM. The concept can be extended to design a multiple peptide substrate labeled with different electroactive reporters for assaying multiple MMPs activities.

Electrochemistry↗
PubMed2006

Trophoblast adhesion of the peri-implantation mouse blastocyst is regulated by integrin signaling that targets phospholipase C.

Integrin signaling modulates trophoblast adhesion to extracellular matrices during blastocyst implantation. Fibronectin (FN)-binding activity on the apical surface of trophoblast cells is strengthened after elevation of intracellular Ca(2+) downstream of integrin ligation by FN. We report here that phosphoinositide-specific phospholipase C (PLC) mediates Ca(2+) signaling in response to FN. Pharmacological agents used to antagonize PLC (U73122) or the inositol phosphate receptor (Xestospongin C) inhibited FN-induced elevation of intracellular Ca(2+) and prevented the upregulation of FN-binding activity. In contrast, inhibitors of Ca(2+) influx through either voltage-gated or non-voltage-gated Ca(2+) channels were without effect. Inhibition of protein tyrosine kinase activity by genistein, but not G-protein inhibition by suramin, blocked FN-induced intracellular Ca(2+) signaling and upregulation of adhesion, consistent with involvement of PLC-gamma. Confocal immunofluorescence imaging of peri-implantation blastocysts demonstrated that PLC-gamma2, but not PLC-gamma1 nor PLC-beta1, accumulated near the outer surface of the embryo. Phosphotyrosine site-directed antibodies revealed phosphorylation of PLC-gamma2, but not PLC-gamma1, upon integrin ligation by FN. These data suggest that integrin-mediated activation of PLC-gamma to initiate phosphoinositide signaling and intracellular Ca(2+) mobilization is required for blastocyst adhesion to FN. Signaling cascades regulating PLC-gamma could, therefore, control a critical feature of trophoblast differentiation during peri-implantation development.

Animals↗
PubMed2006

Isolation, structure, and absolute stereochemistry of platensimycin, a broad spectrum antibiotic discovered using an antisense differential sensitivity strategy.

Fatty acids are essential for survival of bacteria and are synthesized by a series of enzymes including the elongation enzymes, beta-ketoacyl acyl carrier protein synthase I/II (FabF/B). Inhibition of fatty acid synthesis is one of the new targets for the discovery and development of antibacterial agents. Platensimycin (1a) is a novel broad spectrum Gram-positive antibiotic produced by Streptomyces platensis. It was discovered by target-based whole-cell screening strategy using antisense differential sensitivity assay. It inhibits bacterial growth by selectively inhibiting condensing enzyme FabF of the fatty acid synthesis pathway and was isolated by a two-step process, a capture step followed by reversed-phase HPLC. The structure was elucidated by 2D NMR methods and confirmed by X-ray crystallographic analysis of a bromo derivative. It was determined that potential reactivity of the enone moiety does not play a key role in the biological activity of platensimycin. However, cyclohexenone ring conformation renders for the stronger binding interaction with the enzyme. The isolation, structure elucidation, derivatization, and biological activity of 6,7-dihydroplatensimycin are described.

Adamantane↗
PubMed2006

Kinetic behavior of Ti-doped NaAlH4 when cocatalyzed with carbon nanostructures.

The effects of SWNTs, MWNTs, AC, C(60), and G when used as a cocatalyst with Ti on the dehydrogenation and hydrogenation kinetics of NaAlH(4) were investigated for the first time in the important temperature range of 90 to 250 degrees C. All five carbons exhibited significant, sustaining, and synergistic cocatalytic effects on the dehydrogenation and hydrogenation kinetics of Ti-doped NaAlH(4) that persisted through charge and discharge cycling. SWNTs were the best cocatalyst, G was the worst cocatalyst, and all five carbons were inactive as a catalyst unless Ti was present. The carbon most likely was imparting an electronic contribution through the interaction of its facile pi-electrons with Ti through a hydrogen spillover mechanism, which explained why one carbon was better than another one in terms of optimal aromatic character, out-of-plane exposure of pi-electrons, and interaction of pi-bonds with neighboring sheets.

Journal Article↗
PubMed2006

Determination of conformational free energies of peptides by multidimensional adaptive umbrella sampling.

We improve the multidimensional adaptive umbrella sampling method for the computation of conformational free energies of biomolecules. The conformational transition between the alpha-helical and beta-hairpin conformational states of an alanine decapeptide is used as an example. Convergence properties of the weighted-histogram-analysis-based adaptive umbrella sampling can be improved by using multiple replicas in each adaptive iteration and by using adaptive updating of the bounds of the umbrella potential. Using positional root-mean-square deviations from structures of the alpha-helical and beta-hairpin reference states as reaction coordinates, we obtained well-converged free energy surfaces of both the in-vacuum and in-solution decapeptide systems. From the free energy surfaces well-converged relative free energies between the two conformational states can be derived. Advantages and disadvantages of different methods for obtaining conformational free energies as well as implications of our results in studying conformational transitions of proteins and in improving force field are discussed.

Alanine↗
PubMed2006

[Long-term effects of video-assisted thoracoscopic thymectomy for myasthenia gravis: 5-year follow-up of 18 cases].

OBJECTIVE: To evaluate the long-term effects of video-assisted thoracoscopic thymectomy for myasthenia gravis (MG). METHODS: Eighteen MG patients, 7 males and 11 females, aged 33.4 +/- 9.4 (19 - 48), underwent video-assisted thoracoscopic thymectomy by the same surgical group from November 2001 to May 2005. Right side access was used in 14 of them, left side approach was used in 2, and bilateral approach in 1 of them. The thymus and fatty tissue in the front mediastinum were resected. The medical records were reviewed and telephone survey was conducted to understand the effects. The mean follow-up time was 26.4 +/- 10.9 months. RESULTS: VATS was successfully conducted except in 1 case. The bleeding volume was less than 50 ml. The average chest tube drainage time was 2.1 +/- 1.2 days, and the mean hospitalization day was 6.3 +/- 3.1 days. Three of the 18 patients needed temporary mechanical ventilation less than 72 hours, and 2 needed reintubation due to either myasthenic or cholinergic crises. Nine of the 18 patients achieved complete relief (50%) and 6 of them (33.3%) had their symptoms greatly improved, and the symptoms of one case remained stable (5.6%), and the overall effective rate was 83.3%. CONCLUSION: Video-assisted thoracoscopic thymectomy is a safe and effective method for treatment of myasthenia gravis with satisfactory long-term outcomes.

Adult↗
PubMed2006

[A comparison of T3 sympathectomy versus T4 sympathectomy in the treatment of primary palmer hyperhidrosis].

OBJECTIVE: To evaluate the effect and side effect of T(3) versus T(4) sympathectomy in the surgical management of primary palmar hyperhidrosis through prospective multi-center randomized controlled trial. METHODS: From Sep 2004 to Feb 2006, 106 consecutive patients (49 males and 54 females) with primary palmar hyperhidrosis were enrolled in the study and randomly assigned into T(3) or T(4) level sympathectomy groups. 66 patients received T(3) sympathetic chain transection and 37 patients received T(4) sympathetic chain transection. The two groups were comparable in all other parameters. RESULTS: All procedures were carried out successfully without severe morbidity or mortality. After a mean follow-up period of 8.6 months, both groups remained satisfactory in palmar sweating control. The T(4) group had more moisture hands compared with the T(3) branch (54.1% vs 15.2%, P < 0.01), but this didn't compromise the patients' satisfactory. The patients in T(4) group showed significantly less dry hand problems than the patients in the T(3) group (5.4% vs. 25.8%, P < 0.05), and so did compensatory sweating (21.6% vs. 45.6%, P < 0.05). CONCLUSION: The procedure of T(3) or T(4) sympathectomy, both transecting the sympathetic chain in one single position in relatively lower segment, are comparatively effective in the treatment of primary palmar hyperhidrosis, but T(4) sympathectomy shows less side effect.

Adolescent↗
PubMed2006

Regulation of transforming growth factor-beta 1-induced apoptosis and epithelial-to-mesenchymal transition by protein kinase A and signal transducers and activators of transcription 3.

Apoptosis and epithelial-to-mesenchymal transdifferentiation or transition (EMT) are crucial for normal development and body homeostasis. The alterations of these events are closely related to some pathologic processes, such as tumor formation and metastasis, fibrotic diseases of liver and kidney, and abnormal development of embryos. The mechanism that underlies the simultaneously occurring apoptosis and EMT induced by transforming growth factor-beta (TGF-beta) has not been well studied. In this report, we investigated the potential mechanism that underlies TGF-beta1-induced apoptosis and EMT. TGF-beta1-induced apoptosis and EMT were associated with the activation of protein kinase A (PKA) and signal transducers and activators of transcription 3 (STAT3). Inhibition of PKA by specific PKA inhibitor H89 or by PKA inhibitor peptide blocked STAT3 activation and suppressed TGF-beta1-induced apoptosis and EMT. Furthermore, overexpression of a phosphorylation-deficient form of STAT3, but not wild-type STAT3, produced an inhibitory effect on TGF-beta1-induced apoptosis and EMT. The results indicate that PKA is an upstream regulator for TGF-beta1-induced STAT3 activation and plays an important role in TGF-beta1-mediated apoptosis and EMT. These studies provided a new insight into the signaling mechanism underlying the apoptosis and EMT, which could be of importance in understanding some related physiologic and pathologic processes.

Animals↗
PubMed2006

Homing and differentiation of mesenchymal stem cells delivered intravenously to ischemic myocardium in vivo: a time-series study.

Mesenchymal stem cells (MSCs) are potential sources of cells for tissue repair. However, little information is available about the time course of homing and differentiation of systemically delivered MSCs after acute myocardial ischemia (MI). In the present study, MSCs were isolated from male rat bone marrow and expanded in vitro. Female rats were divided randomly into three groups. Three hours after coronary ligation, the transplanted group received an infusion of MSCs through the tail vein; at the same time, a coronary-ligated control group was injected with culture medium, and a normal (unligated) group received MSCs. Homing of MSCs to the heart was assessed by expression of the Y chromosome sry gene using fluorescence in situ hybridization (FISH) at 3 days, 1, 4, and 8 weeks after transplantation. Immunofluorescent staining was used to examine markers for cardiomyocytes, endothelial cells, and smooth muscle cells. Hemodynamics in the hearts was also measured to assess cardiac function. At each time point, sry-positive cells were present in the cardiac tissue in transplanted group but not in the hearts of normal and control group animals. The number of sry-positive cells was significantly higher at 1 week compared to 3 days after transplantation. No significant difference was found in the number of sry-positive cells among those of 1, 4, and 8 weeks after transplantation. At 3 days and 1 week after transplantation, the sry-positive cells in the transplanted group lacked troponin, desmin, smooth muscle alpha-actin, and CD31. At the later time points, cardiomyocytes, smooth muscle cells, and endothelial cells bearing sry were identified in the transplanted group. The cardiac function in transplanted group showed higher improvement at 4 and 8 weeks compared to 1 week after transplantation. Our data suggest that intravenously delivered MSCs are capable of homing toward the ischemic myocardium, and the fastigium of homing appeared around 1 week after MI. The differentiation of MSCs to cardiomyocytes, smooth muscle cells, and endothelial cells shows to be time dependent and arises at 1 to 4 weeks after transplantation.

Animals↗
PubMed2006

Rapid assembly of matrix metalloprotease inhibitors using click chemistry.

[reaction: see text] A panel of 96 metalloprotease inhibitors was assembled using "click chemistry" by reacting eight zinc-binding hydroxamate warheads with 12 azide building blocks. Screens of the bidentate compounds against representative metalloproteases provided discerning inhibition fingerprints, revealing compounds with low micromolar potency against MMP-7. The relative ease and convenience of the strategy in constructing focused chemical libraries for rapid in situ screening of MMPs is thereby demonstrated.

Bacillus↗