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Biomedical subjects

Jing Wang

Publications and source records attributed to Jing Wang.

At least 451 records · Page 25Linked to original sources

[Study on the correlation between the different papillomavirus type and telomerase in cervical cancer].

OBJECTIVE: To define a correlation between different human papillomavirus (HPV) types and telomerase activity in cervical cancer. METHODS: Telomerase activity was detected by TRAP-PCR, and different HPV type was determined by PCR in 83 cervical cancer, 47 cervical intraepithelial neoplasia (CIN) and 10 normal cervix cases. RESULTS: With regard to positive rates of telomerase and HPV 16/18: the results were cervical cancer > CIN > normal cervix, CIN III > CIN I, II; with regard to HPV 6/11 positive rate: the results showed CIN I, II > CIN III. Positive rates of telomerase cervical cancer and HPV were bearing on grading and staging, but they did not correlate with histologic subtypes. Positive rate of HPV 6/11 had nothing to do with grading, staging and histologic patterns. On expression strength of telomerase and HPV 16/18: the results showed cervical cancer > CIN, CIN III > CIN I, II. Regard to HPV 6/11'expression strength: the results showed CIN I, II > CIN III, CIN > cervical carcinoma. CONCLUSION: HPV 16/18 infection seemed to have played an important role in carcinogenesis of cervical lesions by activation of telomerase.

Female↗

[Sphingolipid and apoptosis].

Over the last decade, considerable progress has been made in the study of sphingolipids with the development of biological techniques. Sphingolipids play important roles in diverse physiological process, including cytoskeleton migration, angiogenesis, embryonic development and signal transduction. Except for this, the lastest evidence has suggested that sphingolipids and their metabolite (ceramide, sphingosine, sphingosine 1-phosphate) can induce apoptosis in a wide variety of tumor cell lines such as LoVo HT29, Bel7402, A549, CNE2 cells. This paper is attempted to review the recent advances of investigation into the relationship between sphingolipids and apoptosis.

Animals↗

[Effect of triadimefon on cucumber seedlings growth and their resistance to chilling injury].

Studies on the effects of different concentrations of triadimefon on cucumber seedlings growth and their resistance to chilling injury showed that 20-100 mumol.L-1 triadimefon inhibited the shoot or root length of cucumber seedlings, and increased their root weight or root/shoot ratio and chlorophyll content significantly. After at low temperature for 3 days, a higher chlorophyll content, lower membrane relative permeability and higher SOD activity were observed in the leaves of cucumber seedlings soaked with 10-50 mumol.L-1 triadimefon. 50 mumol.L-1 triadimefon could retard the accumulation of MDA at low temperature stress. It was also observed that 50 mumol.L-1 triadimefon enhanced the accumulation of praline at the first day of chilling treatment. However, higher concentrations(> 100 mumol.L-1) of triadimefon were unfavorable for cucumber seedlings to defense against low temperature. It was thus concluded that triadimefon protected the cucumber seedlings against low temperature.

Cold Temperature↗

[New quantificational indexes in modern study of soil organic matter].

In modern study of soil organic matter, many new quantificational indexes and relevant testing methods, e.g., DOC, WSOC, HWC, ROC, MBC, MBN, PMC, PMN, Glu, Gla, Man, Mur, delta 13C, and CPMI, came forth with deepening study. Because they are disorderly and unsystematic, it is necessary to clarify these indexes. This paper summarized their origin, concept, and testing method, which is of significance in the modern study of soil organic matter.

Organic Chemicals↗

[Effect of PD98059 on Ras-MAPK signal transduction pathway of chronic myelogenous leukemia].

AIM: To study the effect and mechanism of PD98059 on Ras-MAPK signal transduction pathway of chronic myelogenous leukemia. METHODS: K562 cell line was treated by PD98059, cell viability, DNA synthesis, colony formation and MAPK activity of the treated cells were analyzed. RESULTS: The cell viability, DNA synthesis, colony formation and MAPK activity were significantly inhibited by PD98059 (P<0.05), and the inhibitory effect was dose dependent. CONCLUSION: The inhibitory effect of PD98059 was achieved by blocking Ras-MAPK signal transduction pathway which can become a new target in the treatment of CML.

Cell Proliferation↗

[Study on immunoregulatory functions of E.coli heat-labil enterotoxin B subunit].

AIM: To explore the immunoregulatory functions of Escherichia coli heat-labil enterotoxin B subunit(LTB) and its possible mechanism. METHODS: The rLTB in engineering bacteria VSP60 was purified by Sephacryl S-100 gel filtration chromatography. BALB/c mice were immunized nasally with hen egg lysozyme(HEL) alone or in combination with various doses of LTB. After three times of immunization, specific anti-HEL IgG and IgA levels in serum and small intestinal secretory fluid were determined by ELISA. The effects of LTB on alloantigen- and ConA- mediated lymphocyte proliferation reactions were measured by (3)H-TdR incorporation assay. RESULTS: Very weak serum anti-HEL IgG response and no IgA response were detected in mice immunized with HEL alone. However, levels of both serum anti-HEL IgG, IgA and intestinal secretory fluid IgA in mice immunized with various doses of HEL+LTB were higher than those in mice immunized with HEL alone(P<0.001). In-vitro, LTB could obviously inhibit the lymphocyte proliferation induced by mitogen and alloantigen. CONCLUSIONS: The effects of LTB protein on immnune system may be bi-directional. LTB is not only a powerful mucocal immunoadjuvant in-vivo, but also a potent immunosuppressive agent In-vitro.

Animals↗

Src kinase becomes preferentially associated with the VEGFR, KDR/Flk-1, following VEGF stimulation of vascular endothelial cells.

BACKGROUND: The cytoplasmic tyrosine kinase, Src, has been found to play a crucial role in VEGF (vascular endothelial growth factor) - dependent vascular permeability involved in angiogenesis. The two main VEGFRs present on vascular endothelial cells are KDR/Flk-1 (kinase insert domain-containing receptor/fetal liver kinase-1) and Flt-1 (Fms-like tyrosine kinase-1). However, to date, it has not been determined which VEGF receptor (VEGFR) is involved in binding to and activating Src kinase following VEGF stimulation of the receptors. RESULTS: In this report, we demonstrate that Src preferentially associates with KDR/Flk-1 rather than Flt-1 in human umbilical vein endothelial cells (HUVECs), and that VEGF stimulation resulted in an increase of Src activity associated with activated KDR/Flk-1. These findings were determined through immunoprecipitation-kinase experiments and coimmunoprecipitation studies, and were further confirmed by GST-pull-down assays and Far Western studies. However, Fyn and Yes, unlike Src, were found to associate preferentially with Flt-1. CONCLUSIONS: Thus, Src preferentially associates with KDR/Flk-1, rather than with Flt-1, upon VEGF stimulation in endothelial cells. Our findings further highlight the potential significance of upregulated KDR/Flk-1-associated Src activity in the process of angiogenesis, and help to elucidate more clearly the specific roles and mechanisms involving Src family tyrosine kinase in VEGF-stimulated signal transduction events.

CSK Tyrosine-Protein Kinase↗

Design of noncovalent inhibitors of human cathepsin L. From the 96-residue proregion to optimized tripeptides.

A novel series of noncovalent inhibitors of cathepsin L have been designed to mimic the mode of autoinhibition of procathepsin L. Just like the propeptide, these peptide-based inhibitors have a reverse-binding mode relative to a substrate and span both the S' and S subsites of the enzyme active site. In contrast to previous studies in which even moderate truncation of the full-length propeptide led to rapid reduction in potency, these blocked tripeptide-sized inhibitors maintain nanomolar potency. Moreover, these short peptides show higher selectivity (up to 310-fold) for inhibiting cathepsin L over K versus only 2-fold selectivity of the 96-residue propeptide of cathepsin L. A 1.9 A X-ray crystallographic structure of the complex of cathepsin L with one of the inhibitors confirms the designed reverse-binding mode of the inhibitor as well as its noncovalent nature. Enzymatic analysis also shows the inhibitors to be resistant to hydrolysis at elevated concentrations of the enzyme. The mode of inhibition of these molecules provides a general strategy for inhibiting other cathepsins as well as other proteases.

Binding Sites↗

[Attenuation of chronic stress-induced hippocampal damages following physical exercise].

The long-term potentiation (LTP) in the hippocampal dentate gyrus and the plasma glucocorticoids level were observed in rats to study the effects of physical exercise on chronic stress-induced hippocampal damages. Eight-week spontaneous wheel running exercise could attenuate the suppression of LTP induced by 21-day restraint stress, and maintain the normal plasma glucocorticoids levels. It is suggested that long-term physical exercise may protect the hippocampus from stress-induced damages.

Animals↗

Activity-dependent regulation of HCN pacemaker channels by cyclic AMP: signaling through dynamic allosteric coupling.

Signal transduction in neurons is a dynamic process, generally thought to be driven by transient changes in the concentration of second messengers. Here we describe a novel regulatory mechanism in which the dynamics of signaling through cyclic AMP are mediated by activity-dependent changes in the affinity of the hyperpolarization-activated, cation nonselective (HCN) channels for cAMP, rather than by changes in cAMP concentration. Due to the allosteric coupling of channel opening and ligand binding, changes in cellular electrical activity that alter the opening of the HCN channels modify the binding of static, basal levels of cAMP. These changes in ligand binding produce long-lasting changes in channel function which can contribute to the regulation of rhythmic firing patterns.

Action Potentials↗

Inhibition of Kv2.1 voltage-dependent K+ channels in pancreatic beta-cells enhances glucose-dependent insulin secretion.

Voltage-dependent (Kv) outward K(+) currents repolarize beta-cell action potentials during a glucose stimulus to limit Ca(2+) entry and insulin secretion. Dominant-negative "knockout" of Kv2 family channels enhances glucose-stimulated insulin secretion. Here we show that a putative Kv2.1 antagonist (C-1) stimulates insulin secretion from MIN6 insulinoma cells in a glucose- and dose-dependent manner while blocking voltage-dependent outward K(+) currents. C-1-blocked recombinant Kv2.1-mediated currents more specifically than currents mediated by Kv1, -3, and -4 family channels (Kv1.4, 3.1, 4.2). Additionally, C-1 had little effect on currents recorded from MIN6 cells expressing a dominant-negative Kv2.1 alpha-subunit. The insulinotropic effect of acute Kv2.1 inhibition resulted from enhanced membrane depolarization and augmented intracellular Ca(2+) responses to glucose. Immunohistochemical staining of mouse pancreas sections showed that expression of Kv2.1 correlated highly with insulin-containing beta-cells, consistent with the ability of C-1 to block voltage-dependent outward K(+) currents in isolated mouse beta-cells. Antagonism of Kv2.1 in an ex vivo perfused mouse pancreas model enhanced first- and second-phase insulin secretion, whereas glucagon secretion was unaffected. The present study demonstrates that Kv2.1 is an important component of beta-cell stimulus-secretion coupling, and a compound that enhances, but does not initiate, beta-cell electrical activity by acting on Kv2.1 would be a useful antidiabetic agent.

Animals↗

The tyrosine phosphatase PRL-1 localizes to the endoplasmic reticulum and the mitotic spindle and is required for normal mitosis.

PRL-1 is one of three closely related protein-tyrosine phosphatases, which are characterized by C-terminal farnesylation. Recent reports suggest that they are involved in the regulation of cell proliferation and transformation. However, their biological function has not yet been determined. Here we show that PRL-1 mRNA is overexpressed in a number of human tumor cell lines, including HeLa cells. Using immunofluorescence we studied the subcellular localization of endogenous PRL-1, and our results demonstrate that PRL-1 exhibits cell cycle-dependent localization; in non-mitotic HeLa cells, PRL-1 is localized to the endoplasmic reticulum in a farnesylation-dependent manner. In mitotic cells PRL-1 relocalizes to the centrosomes and the spindle apparatus, proximal to the centrosomes, in a farnesylation-independent manner. Conditional expression of a catalytic domain mutant in HeLa cells results in a delay in the progression of cells through mitosis but has no effect on other phases of the cell cycle. Further, expression of a farnesylation site PRL-1 mutant results in mitotic defects, characterized by chromosomal bridges in anaphase and lagging chromosomes, without affecting spindle checkpoint function. Together, these results suggest that PRL-1 function is regulated in a cell cycle-dependent manner and implicate PRL-1 in regulating progression through mitosis, possibly by modulating spindle dynamics.

Amino Acid Sequence↗

A novel immunosuppressive drug, FTY720, prevents the cancer progression induced by cyclosporine.

Cyclosporine A (CsA), the most frequently used immunosuppressive drug, has been reported to induce cancer by a cell-autonomous mechanism. Herein, we report that FTY720, a novel immunosuppressant, prevents CsA-induced alterations in both morphology and cell motility at a low concentration (0.1 microM) and induces the CsA-treated cancer cells to undergo apoptosis at a higher concentration (more than 5 microM). The inhibitory activity of FTY720 is unrelated to the decrease of TGF-beta. We believe that a combination treatment with FTY720 and CsA not only results in a synergistic effect on allografts, but also, reduces the incidence of cancer in transplant patients.

Apoptosis↗

Melt, hydration, and micellization of the PEO-PPO-PEO block copolymer studied by FTIR spectroscopy.

Fourier transform infrared (FTIR) spectroscopy was used to study the conformational changes of the polyethylene oxide-polypropylene oxide-polyethylene oxide (PEO-PPO-PEO) block copolymer, Pluronic P104, in a large concentration range in a polymer-water system as a function of temperature. The melt in which the conformational transition of the PEO blocks occurs gives remarkable changes in the spectral behavior. A small amount of water in Pluronic P104 can induce the PEO block amorphism. The addition of more water only swells the PEO dominant region and gives no significant difference in the conformational structure of the block copolymer in the ordered phases of Pluronic P104-water mixtures. The PPO blocks of Pluronic P104 are hydrated only in a condition of lower temperature and higher water content. The temperature dependent micellization of Pluronic P104 in water was analyzed by a FTIR spectroscopic method. The appearance of the symmetric deformation band of the anhydrous methyl groups at temperature below the CMT indicates the existence of a hydrophobic microenvironment. The appearance of the symmetric deformation band of the hydrated methyl groups at higher temperatures indicates that the micellar core must contain some amount of water. The results of FTIR data show that the proportion of the anhydrous methyl groups increases and water content in the micellar core decreases during the micellization process.

Micelles↗

Syntheses of optically active tetrahydro-1H-pyrrolo[1,2-a]imidazol-2-ones and hexahydroimidazo[1,2-a]pyridin-2(3H)-ones.

The reactions of (2S)-2-amino-2-substituted-N-(4-nitrophenyl)acetamides 16a-c, succindialdehyde (13), and benzotriazole afforded enantiopure (3S,5R,7aR)-5-(1H-1,2,3-benzotriazol-1-yl)-3-substituted-1-(4-nitrophenyl)tetrahydro-1H-pyrrolo[1,2-a]imidazol-2-ones 17a-c, which were converted by sodium borohydride into (3S,7aR)-3-substituted-1-(4-nitrophenyl)tetrahydro-1H-pyrrolo[1,2-a]imidazol-2-ones 18a-c. Chiral (2S)-2-amino-2-substituted-N-(4-methylphenyl)acetamides 12a-d, easily prepared in two steps from N-Boc-alpha-amino acids 10a-d, similarly reacted with glutaraldehyde (20) and benzotriazole to generate 5-benzotriazolyl-3-substituted-hexahydroimidazo[1,2-a]pyridin-2(3H)-ones 21a-d, which were converted by sodium borohydride directly into optically active 3-substituted-hexahydroimidazo[1,2-a]pyridin-2(3H)-ones 22a-d.

Journal Article↗

Modular arrangement and secretion of a multidomain serine protease. Evidence for involvement of proline-rich region and N-glycans in the secretion pathway.

The Limulus Factor C (FC), a multidomain glycoprotein that binds bacterial endotoxin with high affinity, belongs to the serine protease family of the complement and blood coagulation cascade. Here, we provide compelling evidence for the importance of modular arrangement and relevance of the proline-rich region (PRR) and N-glycosylation to the secretion and function of FC. We propose that PRR could be a universal conformational domain that regulates protein folding and targeting. FCs lacking PRR preceding the serine protease domain, were localized intracellularly. Misfolded conformers of the intracellular FCs were more susceptible to trypsin digestion. Glycosylation inhibition studies indicate that the presence but not the exact structure of the N-glycans affects the secretion of FC, although the complexity of glycosylation may influence its endotoxin-induced proteolytic cleavage with resultant enzymatic activity. Disruption of specific N-glycan sites at positions 740, 767, and 912, downstream of the PRR, at or near the serine protease domain, blocks its secretion. Co-expressed molecular chaperones like canine calnexin associates with glycosylated FCs to increase its solubility and secretion level but did not alter their expression profiles. Our results clearly demonstrate that the folding and secretion of a multidomain serine protease like FC are determined by its modular domain arrangement and site-specific N-glycans. The secreted FCs containing the N-terminal portion of FC are able to detect lipopolysaccharide with high sensitivity. We also identified the lectin-like and sushi 4 domains to contribute to the binding of lipopolysaccharide.

Amino Acid Sequence↗