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Biomedical subjects

Ming Jiang

Publications and source records attributed to Ming Jiang.

At least 55 records · Page 3Linked to original sources
PubMed2005

Strategies for constructing polymeric micelles and hollow spheres in solution via specific intermolecular interactions.

We succeeded recently in developing a series of new pathways to polymeric micelles and hollow spheres via intermolecular specific interactions. A new micellization mechanism of block copolymers was realized by using the specific interaction between a low molecular weight compound and one of the blocks in low-polarity solvents. Many more successes have been achieved by our "block copolymer-free" strategies. We are now able to use homopolymers, random copolymers, oligomers, etc. as building blocks to construct noncovalently connected micelles (NCCM), in which the core and shell are connected by hydrogen bonding. Some of such NCCMs are readily converted further into hollow spheres by cross-linking the shell and then switching the medium to one that dissolves the core. Rigid polymer chains and their complementary homopolymers can directly assemble into large hollow spheres thanks to the propensity to parallel packing of the rigid chains. In addition, some of the NCCMs show perfect stimuli-responsive properties. pH-dependent micellization and pH-dependent micelle-hollow-sphere transition are realized in water-soluble graft copolymers driven by complexation and decomplexation between the main chain and grafts.

Journal Article↗
PubMed2005

Selective silencing of viral gene E6 and E7 expression in HPV-positive human cervical carcinoma cells using small interfering RNAs.

The newly discovered phenomenon of RNA interference (RNAi) offers the dual facility of selective viral gene silencing coupled with ease of tailoring to meet genetic variation within the viral genome. Such promise identifies RNAi as an exciting new approach to treat virus-induced diseases, including virus-induced cancers. RNAi can be induced using small interfering RNA (siRNA). Synthetic siRNA targets homologous mRNA for degradation, and this process is highly efficient. Using cervical cancer cells as a model, we demonstrate RNAi for viral oncogenes. Cervical cancer is the second most common cancer in women worldwide and is caused by human papillomavirus (HPV). Silencing of HPV E6 and E7 gene expression was achieved using siRNAs to target the respective viral mRNAs. E6 silencing induced accumulation of cellular p53 protein, transactivation of the cell cycle control p21 gene, and reduced cell growth. By contrast, E7 silencing induced apoptotic cell death. HPV-negative cells appeared to be unaffected by the antiviral siRNAs. Thus siRNA can induce selective silencing of exogenous viral genes in mammalian cells, and the process does not interfere with the recovery of cellular regulatory systems previously inhibited by viral gene expression.

Apoptosis↗
PubMed2005

[RT-PCR detecting NUP98-HOX fusion gene in leukemia].

To investigate whether there are NUP98-HOXA, NUP98-HOXB, NUP98-HOXC, NUP98-HOXD fusion genes in leukemia patients in Xinjiang, cellular total RNA was extracted from the bone marrow mononuclear cells, the formaldehyde-agarose gel electrophoresis was used to judge whether RNA was intact, the 17 RT-PCR primers were designed to amplify the predicted fusion junctions and 412 bp GAPDH was used as an internal control, NUP98-HOXA fusion genes were amplified by nested-PCR following reverse transcription. One-step PCR was performed to amplify the other predicted fusion genes. The results showed that RNA was proved to be intact and expression of GAPDH was found in every sample. However, no predicted fusion transcripts were detected in leukemia patients. In conclusion, no NUP98-HOX fusion genes were detected in the samples from Xinjiang.

Adult↗
PubMed2004

A functional role of postsynaptic density-95-guanylate kinase-associated protein complex in regulating Shank assembly and stability to synapses.

Postsynaptic density (PSD) proteins include scaffold, cytoskeletal, and signaling proteins that structurally and functionally interact with glutamate receptors and other postsynaptic membrane proteins. The molecular mechanisms regulating the assembly of PSD proteins and their associations with synapses are still widely unknown. We investigated the molecular mechanisms of Shank1 targeting and synapse assembly by looking at the function of guanylate kinase-associated protein (GKAP) and PSD-95 interactions. Shank1 when it is not associated to GKAP, which binds to the Shank PSD-95-Discs Large-zona occludens-1 domain, forms filamentous and fusiform structures in which the Src homology 3 domain specifically interacts with the ankyrin repeat domain, thus allowing its multimerization via a novel form of intermolecular interaction. Surprisingly, in both COS-7 cells and hippocampal neurons, GKAP forms insoluble aggregates with Shank that colocalize with heat shock protein 70 and neurofilaments, two markers of the aggresomes in which misfolded proteins accumulate. However, the two proteins are organized in clusters in COS cells and synaptic clusters in neurons when both are overexpressed and associated with wild-type PSD-95, but not with palmitoylation-deficient PSD-95. Synaptic activity in neurons induces the formation of Shank and GKAP intracellular aggregation and degradation. Similarly, the overexpression of a GKAP mutant that is incapable of binding PSD-95 induces Shank aggregation and degradation in neurons. Our data suggest a possible functional and structural role of the PSD-95-GKAP complex in Shank and PSD protein assembly and stability to synapses.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Combined X-ray photoelectron spectroscopy and time-of-flight secondary ion MS surface quantitative analysis of polymer blends with varying mixing thermodynamics.

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) was used to quantitatively correlate to the surface chemical composition determined from XPS in poly(styrene-co-p-hexafluorohydroxyisopropyl-alpha-methyl styrene)/poly(4-vinyl pyridine) (PS(OH)/PVPy) blends or complexes when the p-(hexafluoro-2-hydroxyisopropyl)-alpha-methylstyrene (HFMS) contents in PS(OH) copolymers were gradually increased. It was found that different mixing thermodynamics, such as immiscibility, miscibility, and complexation, have little effect on the quantitative analysis of PS(OH) copolymers in the blends or complexes using TOF-SIMS. In the positive spectra, either the normalized intensities or relative peak intensities can be used to quantitatively analyze the surface HFMS, PS(OH), or PVPy concentration when peaks at m/z = 257, 271, 285, and 373 are used for HFMS, peaks at m/z = 91, 103, 105, 115 for styrene, and peaks at m/z = 132, 195, 209 for PVPy. In the negative spectra, the normalized intensities of peaks characteristic of PVPy seem to be not affected by hydrogen bonding formation and can be used in quantitative analysis, whereas peaks characteristic of HFMS, such as a peak at m/z = 283, cannot be used in quantitative analysis due to enhancement of its secondary ion yield resulting from hydrogen bond formation.

Journal Article↗
PubMed2004

Interaction of apo cytochrome c with sulfonated polystyrene nanoparticles.

Stable nanoparticle dispersion in aqueous solutions was obtained with partially sulfonated polystyrene. The hydrophobic association of the backbone chains and phenyl groups is balanced by the electrostatic repulsion of the sulfonate groups on the particle surface. The size distribution of the sulfonated polystyrene particles in relation to concentration, degree of sulfonation and chain length, and pH was characterized by dynamic laser light-scattering. The structure and morphology of the particles were characterized with fluorescence and atom force microscopy. Highly sulfonated polystyrene particles can form large complex particles with positively charged protein, apo cytochrome c. Dynamic laser light-scattering and atom force microscopy studies show that the size and distribution of the complex particles depend on the relative amount of apo cytochrome c and sulfonated polystyrene. When sulfonated polystyrene is in excess, apo cytochrome c interacts with sulfonated polystyrene particles forming stable complexes and excessive sulfonated polystyrene particles bind to the periphery of the complexes preventing them from further aggregation. When apo cytochrome c is in excess, apo cytochrome c links the complexes forming much larger particles. Fluorescence study demonstrates that the hydrophobicity/hydrophility of the complex particles is relative to the ratio of apo cytochrome c and sulfonated polystyrene, degree of sulfonation, and pH. Apo cytochrome c not only can neutralize the negative charges on the surface of sulfonated polystyrene particles, but may also insert into the cores disrupting the original structure of sulfonated polystyrene particles.

Apoproteins↗
PubMed2004

Approaches to understanding the importance and clinical implications of peroxisome proliferator-activated receptor gamma (PPARgamma) signaling in prostate cancer.

The development and maintenance of the prostate are dependent upon a complex series of interactions occurring between the epithelial and stromal tissues (Hayward and Cunha [2000]: Radiol. Clin. N. Am. 38:1-14). During the process of prostatic carcinogenesis, there are progressive changes in the interactions of the nascent tumor with its surrounding stroma and extracellular matrix. These include the development of a reactive stromal phenotype and the possible promotion, by stromal cells, of epithelial proliferation and loss of differentiated function (Hayward et al. [1996]: Ann. N. Y. Acad. Sci. 784:50-62; Grossfeld et al. [1998]: Endocr. Related Cancer 5:253-270; Rowley [1998]: Cancer Metastasis Rev. 17:411-419; Tuxhorn et al. [2002]: Clin. Cancer Res. 8:2912-2923). Many molecules play an as yet poorly defined role in establishing and maintaining a growth quiescent glandular structure in the adult. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a candidate regulator of prostatic epithelial differentiation and may play a role in restricting epithelial proliferation. PPARgamma agonists are relatively non-toxic and have been used with limited success to treat some prostate cancer patients. We would propose that a more complete understanding of PPARgamma biology, particularly in the context of appropriate stromal-epithelial and host-tumor interactions would allow for the selection of patients most likely to benefit from this line of therapy. In particular, it seems reasonable to suggest that the patients most likely to benefit may be those with relatively indolent low stage disease for whom this line of therapy could be a useful additive to watchful waiting.

Animals↗
PubMed2004

Gel-based application of siRNA to human epithelial cancer cells induces RNAi-dependent apoptosis.

Gene silencing by RNA interference (RNAi) operates at the level of mRNA that is targeted for destruction with exquisite sequence specificity. In principle, any disease-related mRNA sequence is a putative target for RNAi-based therapeutics. To develop this therapeutic potential, it is necessary to develop ways of inducing RNAi by clinically acceptable delivery procedures. Here, we ask if inducers of RNAi can be delivered to human cells via a gel-based medium. RNAi was induced using synthetic small interfering RNAs (siRNAs), which bypass the need for expression vectors and carry the added bonus of high potency and immediate efficacy. Established cultures of human cells of normal and tumor origin were overlaid with an agarose/liposome/siRNA gel formulation without adverse effects on cell viability or proliferation. Epithelial cancer cells (but not normal human fibroblasts) proved vulnerable to specific siRNAs delivered via the agarose/liposome/siRNA formulation. Moreover, proapoptotic siRNAs induced apoptosis of cervical carcinoma cells (treated with human papillomavirus [HPV] E7 siRNA) and of colorectal carcinoma cells (treated with Bcl-2 siRNA). Thus, we demonstrate successful topical gel-based delivery of inducers of RNAi to human epithelial cancer cells. Topical induction of RNAi opens an important new therapeutic approach for treatment of human diseases, including cervical cancer and other accessible disorders.

Administration, Topical↗
PubMed2004

Uniqueness theorems in bioluminescence tomography.

Motivated by bioluminescent imaging needs for studies on gene therapy and other applications in the mouse models, a bioluminescence tomography (BLT) system is being developed in the University of Iowa. While the forward imaging model is described by the well-known diffusion equation, the inverse problem is to recover an internal bioluminescent source distribution subject to Cauchy data. Our primary goal in this paper is to establish the solution uniqueness for BLT under practical constraints despite the ill-posedness of the inverse problem in the general case. After a review on the inverse source literature, we demonstrate that in the general case the BLT solution is not unique by constructing the set of all the solutions to this inverse problem. Then, we show the uniqueness of the solution in the case of impulse sources. Finally, we present our main theorem that solid/hollow ball sources can be uniquely determined up to nonradiating sources. For better readability, the exact conditions for and rigorous proofs of the theorems are given in the Appendices. Further research directions are also discussed.

Algorithms↗
PubMed2004

[Early prediction of efficaciousness after first course of chemotherapy in de novo acute leukemia].

To achieve the complete remission (CR), acute leukemia (AL) patient must get through the period of myeloid ablation after chemotherapy that the white blood cell (WBC) count in peripheral blood decreases rapidly. To observe the relationship of WBC count with therapeutic effectiveness after chemotherapy in previously untreated AL, eighty cases of previously untreated acute leukemia who took the first induction chemotherapy course were analyzed. Blood routine was carried out 2 to 3 times every week while the bone marrow pictures on 12th and 20th day after chemotherapy were observed. 80 patients were divided into 3 groups based on the lowest value of WBC count after chemotherapy: 0.9 x 10(9)/L group. The results showed that the complete remission rates after the first course of chemotherapy were 60 vs 55.6 vs 27.3% respectively in the three groups which WBC counts were 0.9 x 10(9)/L. The total efficaciousness rates were 90 vs 92.6 vs 66.7 respectively in the three groups. The efficaciousness rate of the first two groups significantly differed from the third group (P < 0.01). However, no significant difference was shown between the first and second groups. It is concluded that the leukocyte count after the first course of chemotherapy may be an early indicator to predict the efficaciousness of chemotherapy.

Acute Disease↗
PubMed2004

[Construction of human phage-displayed scFv library and selection of the ScFv against rabies virus].

AIM: To construct a human phage displayed single chain Fv antibody (scFv) library and screen specific scFv against rabies virus. METHODS: Using a phage-display technique, IgVH and IgVL genes were cloned from peripheral blood lymphocytes from three donors immunized with the WISTAR PM strain vaccine. Genes encoding scFv fragments were constructed by random linkage of VH gene and VL gene by SOE PCR, and then the constructed scFv genes were cloned into phagemid vector and transfected into E. coli TG1. The recombinant phages were screened by four rounds of panning with rabies virus vaccine. The positive recombinant phages were sequenced and antigen-binding activity of recombinant scFv was detected by competition ELISA. RESULTS: A human phage-displayed scFv library with about 7 x 10(8) sink size was constructed. A new human scFv was selected, which bound specifically to rabies virus and had higher affinity. CONCLUSION: The results lay a solid foundation for preparation of human engineering antibody to rabies virus reported herein with higher affinity.

Amino Acid Sequence↗
PubMed2004

Identification of differentially expressed genes in clinically distinct groups of serous ovarian carcinomas using cDNA microarray.

To identify changes in gene expression in serous epithelial ovarian cancers (SEOC), we utilized cDNA microarrays consisting of 2382 genes with cancer related properties to analyze tumors from 20 patients with defined clinical out-comes. The significance analysis of microarrays method was used to determine differentially expressed genes, leading to the identification of 134 up-regulated and 231 down-regulated genes overall. By increasing the stringency of the statistical selection criteria, 41 over-expressed and 51 under-expressed genes were identified. The median duration of follow-up of the 20 patients was 16.8 months with a median progression free survival of 7.0 months. We found 11 genes that were differentially over-expressed in patients with recurrent disease, and 3 genes (homo sapiens mRNA for Ins P3 5-phophatase, lipoma HMGIC fusion partner-like 2 and CD63 melanoma 1 antigen) in patients who were dead of disease. Subsequently, we examined the distribution of the differentially expressed genes in the cDNA library database from adult human tumor and normal tissues using the DigiNorthern method to identify a subset of genes with relatively restricted tissue distribution. Finally, protein expression of 5 selected genes were further examined using immunohistochemistry applied on a tissue microarray prepared from an independent panel of 93 SEOC tissues. The results provided validation for 2 under-expressed genes (E2F transcription factor 5 and CK14) and 3 over-expressed genes (Bcl2-like 1, COX-2, CD63). Our study demonstrates differential gene expression in clinically distinct groups of SEOC using cDNA microarray. These genes may potentially be useful as biomarkers and/or targets for therapeutic intervention.

Adult↗
PubMed2004

[Excitotoxic effect of glutamate on the afferent neurons in guinea pigs].

OBJECTIVE: To compare Glu-induced excitotoxic damage to the cochlear afferent neurons and changes of cochlear electrophysiology by directly injecting two different concentrations of glutamate into the inner ear of adult guinea pigs. METHODS: Guinea pigs were injected high doses glutamate (Glu-H,20 mmol/L, 10 microl) and low doses of glutamate (Glu-L, 10 mmol/L, 10 microl) into the perilymph of scala tympani. The compound action potential (CAP) was recorded and pathologic changes were evaluated with light and transmission electronic microscope at various time points after the application of glutamate. Results The thresholds of the CAP of Glu-L group (10 mmoL/L, less than one day) and Glu-H group (20 mmol/ L) were significantly increased compared with those of the normal group (P <0.001). But the thresholds of CAP of glutamate application (10 mmol/L, more than one week) weren't significantly different from those of the normal group (P > 0.05). Some changes of the spiral ganglion cells of the cochlear axis were observed in the 2 drug groups by light microscope. There were some vacuoles in the cell body and condensation of nuclear chromatin, shallow cellar liquid. The ratios of pathological changes between the control group and Glu-H group of different concentrations were notably different (P < 0.05). The observation under transmission electronic microscope found disvolution or necrosis of afferent nerve endings, myelinated nerve fibers, and model spiral ganglion cells. The pathological changes of the Glu-H group were more serious than those of the Glu-L group (10 mmol/L). The pathological changes of the Glu-L group would recover in 4 weeks, but those of the drug group would gradually deteriorate and degeneration would become necrosis. CONCLUSION: The morphologic changes and functional losses of afferent neurons in guinea pigs were caused by glutamate in scala tympani. The low dose (10 mmol/L) had induced reversible damage to cochlear afferent neurons. The high dose (20 mmol/L) had triggered irreversible neurodegeneration.

Action Potentials↗
PubMed2003

Pulmonary malignant granular cell tumor.

BACKGROUND: Malignant granular cell tumor (MGCT) is a rare disease entity. Forty-one well-documented MGCTs have been reported in the world literature. CASE REPORT: This report describes a patient who presented with a MGCT of the lung and reviews the preoperative evaluation, pathologic features and differential diagnosis of the disease. This case represents the first report of resected primary pulmonary MGCT. CONCLUSIONS: Diagnosis of MGCT is based on histology of the primary tumor, immunohistochemistry, and exclusion of tumors that may mimic granular cell tumor.

Journal Article↗
PubMed2003

Protein disregulation in red blood cell membranes of type 2 diabetic patients.

The proteomics analysis was used to search for the membrane proteins related to the type 2 diabetes in human red blood cell (RBC). To improve the solubilization and separation for membrane proteins during two-dimensional electrophoresis (2-DE), several types of chaotropes and surfactants were tested. The optimized condition was then screened. About 1000 protein spots from RBC membranes can be resolved on the 2-D gel. To compare the 2-DE patterns between RBC membranes of type 2 diabetic patients and healthy controls, a total of 42 proteins that were differentially expressed were found. The analysis shows that flotillin-1, a recently discovered membrane protein of RBC lipid rafts, appears to be affected in the disease. The result would be quite interesting because flotillin-1 in adipocytes functions is related to stimulate activation of glucose transporter 4 in response to insulin. Additionally, syntaxin 1C and arginase were also disregulated in patient RBC membranes.

Aged↗