Biomedical subjects

Yang Yang

Publications and source records attributed to Yang Yang.

At least 109 records · Page 6Linked to original sources

PubMed2005

Aberrant methylation in promoter-associated CpG islands of multiple genes in acute lymphoblastic leukemia.

Methylation profile was analyzed in 10 childhood acute lymphoblastic leukemia (ALL) and nine adult ALL cases. Four genes (p15, p16, RARbeta, FHIT) had methylation in both diseases, four genes (p14, Rb, MLH1, DAPK) showed no methylation in both diseases, and the two genes (APC, RIZ) demonstrated methylation only in adult ALL. Methylation of the RARbeta was more frequent in adult ALL than that in childhood ALL (p=0.01). The number of patients with methylation of multiple genes was higher in adult ALL than that in childhood ALL (p=0.006). Moreover, overall frequency of methylation was higher in adult ALL than that in childhood ALL (p=0.01).

Adolescent↗

PubMed2005

Where is the spike generator of the cochlear nerve? Voltage-gated sodium channels in the mouse cochlea.

The origin of the action potential in the cochlea has been a long-standing puzzle. Because voltage-dependent Na+ (Nav) channels are essential for action potential generation, we investigated the detailed distribution of Nav1.6 and Nav1.2 in the cochlear ganglion, cochlear nerve, and organ of Corti, including the type I and type II ganglion cells. In most type I ganglion cells, Nav1.6 was present at the first nodes flanking the myelinated bipolar cell body and at subsequent nodes of Ranvier. In the other ganglion cells, including type II, Nav1.6 clustered in the initial segments of both of the axons that flank the unmyelinated bipolar ganglion cell bodies. In the organ of Corti, Nav1.6 was localized in the short segments of the afferent axons and their sensory endings beneath each inner hair cell. Surprisingly, the outer spiral fibers and their sensory endings were well labeled beneath the outer hair cells over their entire trajectory. In contrast, Nav1.2 in the organ of Corti was localized to the unmyelinated efferent axons and their endings on the inner and outer hair cells. We present a computational model illustrating the potential role of the Nav channel distribution described here. In the deaf mutant quivering mouse, the localization of Nav1.6 was disrupted in the sensory epithelium and ganglion. Together, these results suggest that distinct Nav channels generate and regenerate action potentials at multiple sites along the cochlear ganglion cells and nerve fibers, including the afferent endings, ganglionic initial segments, and nodes of Ranvier.

Action Potentials↗

PubMed2005

Growth and photoluminescence characterization of highly oriented CuI/beta-cyclodextrin hybrid composite film.

A highly (111) oriented CuI/beta-cyclodextrin inorganic/organic composite film on glass substrates was deposited from a dispersion of CuI and beta-cyclodextrin in a mixture of acetonitrile and dimethylformamide (DMF) solvents, in which DMF plays an important role in the orientation of CuI film. The composite film exhibits obviously improved band gap photoluminescence compared with that of the pure CuI film due to the passivation of iodine-related defect sites by beta-cyclodextrin matrix. This result indicates that the optical properties of CuI film can be easily adjusted by the formation of composite film with proper ligand agents.

Journal Article↗

PubMed2005

Molecular imaging using labeled donor tissues reveals patterns of engraftment, rejection, and survival in transplantation.

Tissue regeneration and transplantation of solid organs involve complex processes that can only be studied in the context of the living organism, and methods of analyzing these processes in vivo are essential for development of effective transplantation and regeneration procedures. We utilized in vivo bioluminescence imaging (BLI) to noninvasively visualize engraftment, survival, and rejection of transplanted tissues from a transgenic donor mouse that constitutively expresses luciferase. Dynamic early events of hematopoietic reconstitution were accessible and engraftment from as few as 200 transplanted whole bone marrow (BM) cells resulted in bioluminescent foci in lethally irradiated, syngeneic recipients. The transplantation of autologous pancreatic Langerhans islets and of allogeneic heart revealed the tempo of transplant degeneration or immune rejection over time. This imaging approach is sensitive and reproducible, permits study of the dynamic range of the entire process of transplantation, and will greatly enhance studies across various disciplines involving transplantation.

Actins↗

PubMed2005

Osteoblasts generate harder, stiffer, and more delamination-resistant mineralized tissue on titanium than on polystyrene, associated with distinct tissue micro- and ultrastructure.

UNLABELLED: This study revealed that osteoblasts generate harder, stiffer, and more delamination-resistant mineralized tissue on titanium than on the tissue culture polystyrene, associated with modulated gene expression, uniform mineralization, well-crystallized interfacial calcium-phosphate layer, and intensive collagen deposition. Knowledge of this titanium-induced alteration of osteogenic potential leading to enhanced intrinsic biomechanical properties of mineralized tissue provides novel opportunities and implications for understanding and improving bone-titanium integration and engineering physiomechanically tolerant bone. INTRODUCTION: Bone-titanium integration is a biological phenomenon characterized by continuous generation and preservation of peri-implant bone and serves as endosseous anchors against endogenous and exogenous loading, of which mechanisms are poorly understood. This study determines the intrinsic biomechanical properties and interfacial strength of cultured mineralized tissue on titanium and characterizes the tissue structure as possible contributing factors in biomechanical modulation. MATERIALS AND METHODS: Rat bone marrow-derived osteoblastic cells were cultured either on a tissue culture-grade polystyrene dish or titanium-coated polystyrene dish having comparable surface topography. Nano-indentation and nano-scratch tests were undertaken on mineralized tissues cultured for 28 days to evaluate its hardness, elastic modulus, and critical load (force required to delaminate tissue). Gene expression was analyzed using RT-PCR. The tissue structural properties were examined by scanning electron microscopy (SEM), collagen colorimetry and localization with Sirius red stain, mineral quantification, and localization with von Kossa stain and transmission electron microscopy (TEM). RESULTS: Hardness and elastic modulus of mineralized tissue on titanium were three and two times greater, respectively, than those on the polystyrene. Three times greater force was required to delaminate the tissue on titanium than that on the polystyrene. SEM of the polystyrene culture displayed a porous structure consisting of fibrous and globular components, whereas the titanium tissue culture appeared to be uniformly solid. Cell proliferation was remarkably reduced on titanium. Microscopic observations revealed that the mineralized tissue on titanium was composed of uniform collagen-supported mineralization from the titanium interface to the outer surface, with intensive collagen deposition at tissue-titanium interface. In contrast, tissue on the polystyrene was characterized by collagen-deficient mineralization at the polystyrene interface and calcium-free collagenous matrix formation in the outer tissue area. Such characteristic microstructure of titanium-associated tissue was corresponded with upregulated gene expression of collagen I and III, osteopontin, and osteocalcin mRNA. Cross-sectional TEM revealed the apposition of a high-contrast and well-crystallized calcium phosphate layer at the titanium interface but not at the polystyrene interface. CONCLUSIONS: Culturing osteoblasts on titanium, compared with polystyrene, enhances the hardness, elastic modulus, and interfacial strength of mineralized tissue to a higher degree. Titanium per se possesses an ability to alter cellular phenotypes and tissue micro- and ultrastructure that result in enhanced intrinsic biomechanical properties of mineralized tissue.

Animals↗

PubMed2005

Prevention of graft-versus-host disease by a novel immunosuppressant, (5R)-5-hydroxytriptolide (LLDT-8), through expansion of regulatory T cells.

(5R)-5-hydroxytriptolide (LLDT-8) is a new compound derived from triptolide, which is the major immunosuppressive fraction of Tripterygium wilfordii Hook. F (TWHF). In this study, we demonstrated that administration of LLDT-8 (1 mg/kg/day, p.o.) effectively prevented weight loss and death induced by allo-BMT (BLAB/c, H-2d to C57BL/6, H-2b), and extended survival in allo-BMT model of aGVHD. Following days 7 to 28 after allo-BMT, the allogeneic graft survived by increasing the number of engrafted cells (H-2d) in spleens of recipient mice with LLDT-8 treatment. To construe the immunosuppressive effects of LLDT-8, the splenocytes (H-2d) of LLDT-8 treated recipients (H-2b) were tested for the proliferative responses to donor antigen (H-2d), host antigen (H-2b) and mitogen (ConA) stimulations, respectively, the results indicated that LLDT-8 induced the T cells' unresponsiveness to donor and host antigens, while still maintaining response to ConA; Compared with the vehicle group of GVHD mice, administration of LLDT-8 significantly inhibited T cells to produce IFN-gamma with or without host antigen or ConA stimulation. Further studies indicated LLDT-8 had a normalizing effect on the ratio of CD4+/CD8+ T cells, and increased CD4+CD25+ T regulatory cells with the Foxp3 expression in splenocytes from LLDT-8 treated mice. The results outline the great potential of LLDT-8 as a therapeutic tool to induce suppression in GVHD.

Animals↗

PubMed2005

Lack of chemokine receptor CCR5 promotes murine fulminant liver failure by preventing the apoptosis of activated CD1d-restricted NKT cells.

Fulminant liver failure (FLF) consists of a cascade of events beginning with a presumed uncontrolled systemic activation of the immune system. The etiology of FLF remains undefined. In this study, we demonstrate that CCR5 deficiency promotes the development of acute FLF in mice following Con A administration by preventing activated hepatic CD1d-restricted NKT cells (but not conventional T cells) from dying from activation-induced apoptosis. The resistance of CCR5-deficient NKT cells from activation-induced apoptosis following Con A administration is not due to a defective Fas-driven death pathway. Moreover, FLF in CCR5-deficient mice also correlated with hepatic CCR5-deficient NKT cells, producing more IL-4, but not IFN-gamma, relative to wild-type NKT cells. Furthermore, FLF in these mice was abolished by IL-4 mAb or NK1.1 mAb treatment. We propose that CCR5 deficiency may predispose individuals to the development of FLF by preventing hepatic NKT cell apoptosis and by regulating NKT cell function, establishing a novel role for CCR5 in the development of this catastrophic liver disease that is independent of leukocyte recruitment.

Animals↗

PubMed2005

Neurotrophin releasing single and multiple lumen nerve conduits.

Tissue engineering strategies for nerve repair employ polymer conduits termed guidance channels and bridges to promote regeneration for peripheral nerve injury and spinal cord injury, respectively. An approach for fabrication of nerve conduits with single and multiple lumens capable of controlled release of neurotrophic factors was developed. These conduits were fabricated from a mixture of poly(lactide-co-glycolide) (PLG) microspheres and porogen (NaCl) that was loaded into a mold and processed by gas foaming. The porosity and mechanical properties of the constructs were regulated by the ratio of porogen to polymer microsphere. The neurotrophin, nerve growth factor (NGF), was incorporated into the conduit by either mixing the protein with microspheres or encapsulating the protein within microspheres prior to gas foaming. A sustained release was observed for at least 42 days, with the release rate controlled by method of incorporation and polymer molecular weight. Released NGF retained its bioactivity, as demonstrated by its ability to stimulate neurite outgrowth from primary dorsal root ganglion (DRG). In vivo results indicate that conduits retain their original architecture, and allow for cellular infiltration into the channels. Polymer conduits with controllable lumen diameters and protein release may enhance nerve regeneration by guiding and stimulating neurite outgrowth.

Absorbable Implants↗

PubMed2005

CNP is required for maintenance of axon-glia interactions at nodes of Ranvier in the CNS.

Axoglial interactions underlie the clustering of ion channels and of cell adhesion molecules, regulate gene expression, and control cell survival. We report that Cnp1-null mice, lacking expression of the myelin protein cyclic nucleotide phosphodiesterase (CNP), have disrupted axoglial interactions in the central nervous system (CNS). Nodal sodium channels (Nav) and paranodal adhesion proteins (Caspr) are initially clustered normally, but become progressively disorganized with age. These changes are characterized by mislocalized Caspr immunostaining, combined with a decrease of clustered Na+ channels, and occur before axonal degeneration and microglial invasion, both prominent in older Cnp1-null mice. We suggest that CNP is a glial protein required for maintaining the integrity of paranodes and that disrupted axoglial signaling at this site underlies progressive axonal degeneration, observed later in the CNS of Cnp1-null mice.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

PubMed2005

Extraction and proteomic analysis of proteins from normal and multiple sclerosis postmortem brain.

In this study, a reproducible fractionation procedure was developed to reduce levels of the abundant cytoskeletal proteins that are present in normal and pathological central nervous system (CNS) tissues. The fractionation and proteomic analysis techniques employed greatly facilitated comparison of the spectrum of proteins in normal postmortem brain with proteins in samples from patients with multiple sclerosis, an inflammatory demyelinating disease in which complex changes in protein expression occur as lesions develop. This approach may be of value for the proteomic identification and quantitation of proteins which undergo disease-related changes in CNS disorders, and also for protein expression studies on normal adult and developing CNS tissues.

Aged↗

PubMed2005

Microcalorimetry is a sensitive method for studying the effect of nucleotide mutation on promoter activity.

Microcalorimetric method was successfully used to study the effect of nucleotide mutations on promoter activity and identify the important nucleotide necessary for the promoter function in Escherichia coli. The thermokinetic parameters, such as k, I and IC(50), were calculated from the metabolic power-time curves obtained by microcalorimetric measurement using the TAM air Isothermal Microcalorimeter (manufactured by Thermometric AB company of Sweden). Analysis of these data revealed that different nucleotide mutations in -10 box sequence of RM07 fragment had different effect on the promoter activity. Our research also suggest that the microcalorimetric method is a very sensitive and easily performed method for investigation of promoter mutation.

Calorimetry↗

PubMed2005

Chemical composition and antimicrobial activity of the essential oils of Chrysanthemum indicum.

Three essential oils from three samples: fresh, air-dried and processed flowers of Chrysanthemum indicum, obtained by hydrodistillation, were analyzed by GC-MS. The results show that major constituents of the three oils were 1,8-cineole, camphor, borneol and bornyl acetate, but the percentage of these compounds varied greatly because of the processing of flowers. The antimicrobial activity of essential oils from air-dried and processed flowers was evaluated against 15 microorganisms including three yeasts and seven clinical isolated strains using disc paper and broth microdilution methods. Our results show that both essential oils possessed significant antimicrobial effect, however, some difference in antimicrobial activity between two oils was observed for several microorganisms, which was attributed to the variation in percentage of the components. With higher percentage of camphor, the oil of the processed flowers exhibited, in many cases, greater bacteriostatic activity than that of the air-dried ones.

Anti-Bacterial Agents↗

PubMed2005

The guanine nucleotide exchange factor p63RhoGEF, a specific link between Gq/11-coupled receptor signaling and RhoA.

The monomeric GTPase RhoA, which is a key regulator of numerous cellular processes, is activated by a variety of G protein-coupled receptors, through either G12 or G(q) family proteins. Here we report that p63RhoGEF, a recently identified RhoA-specific guanine nucleotide exchange factor, enhances the Rho-dependent gene transcription induced by agonist-stimulated G(q/11)-coupled receptors (M3-cholinoceptor, histamine H1 receptor) or GTPase-deficient mutants of G alpha(q) and G alpha11. We further demonstrate that active G alpha(q) or G alpha11, but not G alpha12 or G alpha13, strongly enhances p63RhoGEF-induced RhoA activation by direct protein-protein interaction with p63RhoGEF at its C-terminal half. Moreover, the activation of p63RhoGEF by G alpha(q/11) occurs independently of and in competition to the activation of the canonical G alpha(q/11) effector phospholipase C beta. Therefore, our results elucidate a new signaling pathway by which G alpha(q/11)-coupled receptors specifically induce Rho signaling through a direct interaction of activated G alpha(q/11) subunits with p63RhoGEF.

Animals↗

PubMed2005

Methylation analysis of the adenomatous polyposis coli (APC) gene in adult T-cell leukemia/lymphoma.

We investigated methylation status of the adenomatous polyposis coli (APC) gene in adult T-cell leukemia/lymphoma (ATL). APC methylation was found in 15 of 31 (48%) primary samples, and 2 of 4 (50%) ATL cell lines. Methylation of the APC gene occurred more frequently in acute ATL (12/21) (57%) than chronic ATL (1/8) (13%) (P = 0.03). APC was not expressed in the APC-methylated ATL cell line ST1. Demethylation with 5-azacytidine treatment restored APC expression in the ST1 cell line. Our data show that hypermethylation of the APC gene is involved in the pathogenesis of ATL.

Adenomatous Polyposis Coli Protein↗

PubMed2005

Polyaniline nanofiber/gold nanoparticle nonvolatile memory.

A nonvolatile plastic digital memory device based on nanofibers of the conjugated polymer polyaniline decorated with gold nanoparticles is reported. The device has a simple structure consisting of the plastic composite film sandwiched between two electrodes. An external bias is used to program the ON and OFF states of the device that are separated by a 3-orders-of-magnitude difference in conductivity. ON-OFF switching times of less than 25 ns are observed by electrical pulse measurements. The devices possess prolonged retention times of several days after they have been programmed. Write-read-erase cycles are also demonstrated. The switching mechanism is attributed to an electric-field-induced charge transfer from the polyaniline nanofibers to the gold nanoparticles. The active polymer layer is created by growing nanometer size gold particles within 30-nm-diameter polyaniline nanofibers using a redox reaction with chloroauric acid. This device combines two exciting research areas--nanoparticles and conducting polymers--to form a novel materials system with unique functionality.

Aniline Compounds↗

PubMed2005

HIV-1 protease inhibitor induces growth arrest and apoptosis of human prostate cancer LNCaP cells in vitro and in vivo in conjunction with blockade of androgen receptor STAT3 and AKT signaling.

This study found that the HIV-1 protease inhibitor nelfinavir (NFV) induced growth arrest and apoptosis of human prostate cancer cells (LNCaP, DU145 and PC-3 cells), as measured by MTT and terminal deoxyribonucleotide transferase-mediated dUTP nick end labeling (TUNEL) assays, respectively, on the third day of culture. In addition, NFV blocked androgen receptor (AR) signaling in association with downregulation of nuclear levels of AR in LNCaP cells as measured by reporter assay and western blot analysis. As expected, NFV downregulated the level of the AR target molecule prostate specific antigen in these cells. Moreover, NFV disrupted STAT3 signaling; protease inhibitors blocked interleukin-6-induced phosphorylation of STAT3 and inhibited STAT3 DNA binding activity in LNCaP and DU145 cells, as measured by western blot analysis and enzyme-linked immunosorbent assay (ELISA), respectively. Furthermore, NFV blocked AKT signaling in prostate cancer cells as measured by kinase assay with glycogen synthase kinase-3alpha/beta as a substrate. Importantly, NFV inhibited the proliferation of LNCaP cells presented as tumor xenografts in BALB/c nude mice without side-effects. Taken together, NFV inhibited the proliferation of prostate cancer cells in conjunction with blockade of signaling by AR, STAT3, and AKT, suggesting that this family of compounds might be useful for the treatment of individuals with prostate cancer.

Animals↗

PubMed2005

Expression and comparative analysis of genes encoding outer membrane proteins LipL21, LipL32 and OmpL1 in epidemic leptospires.

Leptospiral outer membrane proteins (OMPs) are highly conserved in different species, and play an essential role in the development of new immunoprotection and serodiagnosis strategies. The genes encoding LipL21, LipL32 and OmpL1 were cloned from the complete genome sequence of Leptospira interrogans serovar lai strain Lai and expressed in vitro. Sequence comparison analysis revealed that the three genes were highly conserved among distinct epidemic leptospires, including three major epidemic species Leptospira interrogans, Leptospira borgpetersenii and Leptospira weilii, in China. Immunoblot analysis was further performed to scrutinize 15 epidemic Leptospira reference strains using the antisera of the recombinant OMPs. Both immunoblot assay and reverse transcription-polymerase chain reaction demonstrated that these three OMPs were conservatively expressed in pathogenic L. interrogans strains and other pathogenic leptospires. Additionally, the use of these recombinant OMPs as antigens in enzyme-linked immunosorbent assay (ELISA) for serodiagnosis of leptospirosis was evaluated. The recombinant LipL32 and OmpL1 proteins showed a high degree of ELISA reactivity with sera from patients infected with L. interrogans strain Lai and other pathogenic leptospires. These results may contribute to the identification of candidates for broad-range vaccines and immunodiagnostic antigens in further research.

Antigens, Bacterial↗

PubMed2005

Gene and protein expression profiling of the microvascular compartment in experimental autoimmune encephalomyelitis in C57Bl/6 and SJL mice.

Dysfunction of the blood-brain barrier (BBB) is a hallmark of inflammatory diseases of the central nervous system (CNS) such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). The molecular mechanisms leading to BBB breakdown are not well understood. In order to find molecules involved in this process, we used oligonucleotide microarrays and proteomics to analyze gene and protein expression of the microvascular compartment isolated from brains of C57Bl/6 and SJL/N mice afflicted with EAE and the microvascular compartment isolated from healthy controls. Out of the 6500 known genes and expressed sequence tags (ESTs) studied, expression of 288 genes was found to be changed. Of these genes 128 were altered in the microvascular compartment in both EAE models. Six proteins were identified to be present at altered levels. In addition to the expected increased expression of genes coding for molecules involved in leukocyte recruitment, genes not yet ascribed to EAE pathogenesis were identified. Thus, proteomics and gene array screens of the microvascular compartment are valid approaches, that can be used to define novel candidate molecules involved in EAE pathogenesis at the level of the BBB.

Animals↗