Yan Yu | The University of New South Wales (original) (raw)

Papers by Yan Yu

The Spine Journal, 2014

BACKGROUND CONTEXT: The ideal tissue-engineered solution for any bone graft substitute is to assi... more BACKGROUND CONTEXT: The ideal tissue-engineered solution for any bone graft substitute is to assist in the rapid formation of bone and facilitate fusion. PURPOSE: The present study aims to evaluate this E-BMP-2 (Escherichia coli-derived human bone morphogenetic protein-2) in ovine posterolateral lumbar fusion (PLF) to examine the influence of dose and overall performance in a model with similar graft size and diffusive challenges to the human. STUDY DESIGN/SETTING: In vivo large animal model study. METHODS: An adult ovine PLF was performed in 30 animals with groups of E-BMP-2 with a beta-tricalcium phosphate (b-TCP) carrier at three different dosages, b-TCP alone, and autograft from the iliac crest. The fusions were assessed by radiography (X-ray and microcomputed tomography), mechanical testing, and hard-tissue histology with bone labels at 6, 8, and 10 weeks along with routine paraffin histology at 12 weeks. RESULTS: Results showed increasing new bone and fusion rate with E-BMP-2 dose, whereas b-TCP alone was largely resorbed and did not achieve fusion in this model at 12 weeks. Autograft showed similar grading for the amount of bone between the transverse processes but a lower fusion rate than b-TCP/E-BMP-2 groups. Bone labels revealed new bone formation at all time points for the E-BMP2 groups, whereas the autograft group showed active bone formation at 10 weeks. Betatricalcium phosphate displayed reliable incorporation into the decorticated host bone, whereas limited new bone was found between the transverse processes. At the center of the fusion mass, increased E-BMP-2 dose led to increased incorporation of b-TCP by new bone. CONCLUSIONS: These results suggest that E-BMP-2 was capable of producing posterolateral fusion in the ovine model that is equal to or superior to autologous graft in terms of fusion rate and mechanical strength. E-BMP-2 dose had considerable influence on b-TCP granule resorption. Ó

Frontiers in Surgery, 2014

Appropriate well-characterized bone defect animal models remain essential for preclinical researc... more Appropriate well-characterized bone defect animal models remain essential for preclinical research. This pilot study demonstrates a relevant animal model for cancellous bone defect healing. Three different defect diameters (8, 11, 14 mm) of fixed depth (25 mm) were compared in both skeletally immature (18-month-old) and aged sheep (5-year-old). In each animal, four defects were surgically created and placed in the cancellous bone of the medial distal femoral and proximal tibial epiphyses bilaterally. Animals were euthanized at 4 weeks post-operatively to assess early healing and any biological response. Defect sites were graded radiographically, and new bone formation quantified using µCT and histomorphometry. Fibrous tissue was found within the central region in most of the defects with woven bone normally forming near the periphery of the defect. Bone volume fraction [bone volume (BV)/TV] significantly decreased with an increasing defect diameter. Actual BV, however, increased with defect diameter. Bone ingrowth was lower for all defect diameters in the aged group. This pilot study proposes that the surgical creation of 11 mm diameter defects in the proximal tibial and distal femoral epiphyses of aged sheep is a suitable large animal model to study early healing of cancellous bone defects. The refined model allows for the placement of four separate bone defects per animal and encourages a reduction in animal numbers required for preclinical research.

The British journal of radiology, Jan 17, 2015

The study was aimed to evaluate the precision of Elekta 4D cone-beam computed tomography (CBCT) b... more The study was aimed to evaluate the precision of Elekta 4D cone-beam computed tomography (CBCT) based automatic dual image registrations using different landmarks for clipbox for radiation treatment of lung cancer. Thirty 4D CBCT scans from fifteen patients were studied. 4D CBCT images were registered with reference CT images using dual image registration: a clipbox registration and a mask registration. The image registrations performed in clinic using a physician-defined clipbox, which were reviewed by physicians, were taken as the standard. Studies were conducted to evaluate the automatic dual registrations using three kinds of landmarks for clipbox: spine, spine plus internal target volume (ITV), and lung (including as much of the lung as possible). Translational table shifts calculated from the automatic registrations were compared with those of the standard. The mean of the table shift differences in the lateral direction were: 0.03 cm, 0.03 cm, and 0.03 cm, for clipbox based o...

Oncotarget, Jan 29, 2015

The combination of time and order-dependent chemotherapeutic strategies has demonstrated enhanced... more The combination of time and order-dependent chemotherapeutic strategies has demonstrated enhanced efficacy in killing cancer cells while minimizing adverse effects. However, the precise mechanism remains elusive. Our results showed that pre-treatment of MCF-7 and MDA-MB-468 cells with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib or lapatinib significantly enhanced the cytotoxic effects of DNA-damaging agents compared to coadministration of the EGFR inhibitor and DNA-damaging agent. Sequential application of erlotinib and doxorubicin increased activated caspase-8 by promoting pro-caspase-8 homodimerization and autocatalytical cleavage, whereas coadministration did not. We found that EGFR inhibitors promoted pro-caspase-8 homodimerization by inhibiting ERK pathway signaling, while doxorubicin promoted it. Our data highlight that ERK has the potential to inhibit the formation of pro-caspase-8 homodimers by phosphorylating pro-caspase-8 at S387. In conclus...

The American journal of pathology, Jan 5, 2015

Cellular stress response 1 (CSR1) is a tumor suppressor gene whose expression was frequently down... more Cellular stress response 1 (CSR1) is a tumor suppressor gene whose expression was frequently down-regulated in prostate cancer. The mechanism of its down-regulation, however, is not clear. Here, we show that the 3' untranslated region of CSR1 contains a target site of miR-650. High level of miR-650 was found in prostate cancer samples and cell lines. Degradation of miR-650 by specific inhibitor dramatically increased the expression levels of CSR1. Interaction between miR-650 and its target site in the 3' untranslated region was validated through luciferase reporter system. Mutation at the target site completely abrogated the activity of miR-650 on the 3' untranslated region of CSR1. Inhibition of miR-650 reversed the expression suppression of CSR1, suppressed colony formation, and blocked cell cycle entry to the S phase of both PC3 and DU145 cells. Animal model showed significant decrease of tumor volume, rate of metastasis, and mortality of severe combined immunodeficie...

The American journal of pathology, Jan 8, 2015

Fusion transcript formation is one of the fundamental mechanisms that drives the development of p... more Fusion transcript formation is one of the fundamental mechanisms that drives the development of prostate cancer. Because of the advance of high-throughput parallel sequencing, many fusion transcripts have been discovered. However, the discovery rate of fusion transcripts specific for prostate cancer is lagging behind the discoveries made on chromosome abnormalities of prostate cancer. Recent analyses suggest that many fusion transcripts are present in both benign and cancerous tissues. Some of these fusion transcripts likely represent important components of normal gene expression in cells. It is necessary to identify the criteria and features of fusion transcripts that are specific for cancer. In this review, we discuss optimization of RNA sequencing depth for fusion transcript discovery and the characteristics of fusion transcripts in normal prostate tissues and prostate cancer. We also propose a new classification of cancer-specific fusion transcripts on the basis of their tail g...

The Journal of trauma, 1997

To determine the influence of pretreatment with selective decontamination of the digestive tract ... more To determine the influence of pretreatment with selective decontamination of the digestive tract (SDD) on systemic immunosuppression, and the relationship between bacteria/endotoxin translocation and abnormalities of immune function in thermally injured rats. Animals were subjected to a 40% full-thickness scald injury, and divided into SDD-treated and control groups. The treatment group received SDD (polymyxin E, tobramycin, and 5-flucytosine) by gavage twice daily for 3 days before the experiment and continued for 5 days after thermal injury. The control group was given the same amount of water. The parameters reflecting cell-mediated immunity, including splenocyte proliferation in response to mitogens, interleukin 2 (IL-2) production, and lymphocyte subpopulation, were measured before injury and 1 and 5 days after burn, respectively. Thermal injury resulted in marked reduction in splenocyte proliferative response to T-cell mitogens, IL-2 production, and T-helper/suppressor cells (...

Molecular Crystals and Liquid Crystals, 2009

Phospholipid-nanoparticle constructs, formed by allowing nanoparticles to adsorb to the outer lea... more Phospholipid-nanoparticle constructs, formed by allowing nanoparticles to adsorb to the outer leaflet of liposomes, are found to be stabilized against fusion with one another. Here, through single-particle tracking by epifluorescence microscopy, we explore their use as novel colloidal particles -flexible and hollow colloidal particles that contrast strikingly with colloids of the conventional type. At the singleliposome level, the distribution of diffusion coefficients is quantified. Biomolecular function is addressed through experiments in which we explore the access of receptor to liposome-immobilized ligand, finding that receptor binding persists over a range of nanoparticle surface coverage where liposome fusion and large-scale aggregation is prevented. This opens the door to designing newer and more flexible types of tailor-made materials with desirable functionality.

Acta pharmacologica Sinica, 2014

The receptor of advanced glycation end products (RAGE) participates in a variety of pathophysiolo... more The receptor of advanced glycation end products (RAGE) participates in a variety of pathophysiological processes and inflammatory responses. The aim of this study was to investigate the therapeutic potential of an anti-RAGE neutralizing antibody for severe thermal injury in rats, and to determine whether the treatment worked via modulating cellular immune function. Full-thickness scald injury was induced in Wistar rats, which were treated with the anti-RAGE antibody (1 mg/kg, iv) at 6 h and 24 h after the injury. The rats were sacrificed on d 1, 3, 5, and 7. Blood and spleen samples were harvested to monitor organ function and to analyze dendritic cell (DC) and T cell cytokine profiles. The survival rate was analyzed up to d 7 after the injury. Administration of the antibody significantly increased the 7 d survival rate in thermally injured rats (6.67% in the model group; 33.33% in anti-RAGE group). Treatment with the antibody also attenuated the multiple organ dysfunction syndrome ...

$Research paper thumbnail of TGF-beta, BMPS, and their signal transducing mediators, Smads, in rat fracture healing$

Journal of biomedical materials research, Jan 5, 2002

Smads are cytoplasmic signal transducers of transforming growth factor-beta (TGF-beta) and bone m... more Smads are cytoplasmic signal transducers of transforming growth factor-beta (TGF-beta) and bone morphogenetic proteins (BMPs). Their relation to fracture healing is unknown. This study examined the temporal protein expression of Smads, together with TGF-beta and BMPs, using immunohistochemistry in a rodent fracture model. Over-expression of TGF-beta, BMPs-2, 4, and 7, common-mediator Smad (Smad4), and receptor-regulated Smads (Smads1, 2, 3, and 5) versus lower levels of inhibitory Smad (Smad6), were detected at day 3 in osteogenic cells in the thickened periosteum and bone marrow at the fracture sites. At day 10, Smad6 increased dramatically, Smad2, Smad3, and Smad4 remained elevated while Smad1 and Smad5 decreased in the fracture callus. Smad7 was expressed only in vascular endothelial cells. By day 28, when new bone had replaced the fracture callus, all the protein regulators decreased, approaching control levels. During fracture healing, the expression patterns of Smads1 and 5 we...

Cancer research, 2007

Glutathione peroxidase 3 is a selenium-dependent enzyme playing a critical role in detoxifying re... more Glutathione peroxidase 3 is a selenium-dependent enzyme playing a critical role in detoxifying reactive oxidative species and maintaining the genetic integrity of mammalian cells. In this report, we found that the expression of glutathione peroxidase 3 (GPx3) was widely inactivated in prostate cancers. Complete inactivation of GPx3 correlates with a poor clinical outcome. Deletions (hemizygous and homozygous) of GPx3 gene are frequent in prostate cancer samples, occurring in 39% of the samples studied. The rate of methylation of the GPx3 exon 1 region in prostate cancer samples reaches 90%. Overexpression of GPx3 in prostate cancer cell lines induced the suppression of colony formation and anchorage-independent growth of PC3, LNCaP, and Du145 cells. PC3 cells overexpressing GPx3 reduced invasiveness in Matrigel transmigration analysis by an average of 2.7-fold. Xenografted PC3 cells expressing GPx3 showed reduction in tumor volume by 4.8-fold, elimination of metastasis (0/16 versus ...

The Journal of biological chemistry, Jan 16, 2015

Miniature chromosome maintenance 7 (MCM7) is an essential component of DNA replication licensing ... more Miniature chromosome maintenance 7 (MCM7) is an essential component of DNA replication licensing complex. Recent studies indicate that MCM7 is amplified and overexpressed in a variety of human malignancies. In this report, we show that MCM7 binds SF3B3. The binding motif is located in the N terminus (amino acids 221-248) of MCM7. Knockdown of MCM7 or SF3B3 significantly increased unspliced RNA of epidermal growth factor receptor, platelet-derived growth factor receptor, and c-Met. A dramatic drop of reporter gene expression of the oxytocin exon 1-intron-exon 2-EGFP construct was also identified in SF3B3 and MCM7 knockdown PC3 and DU145 cells. The MCM7 or SF3B3 depleted cell extract failed to splice reporter RNA in in vitro RNA splicing analyses. Knockdown of SF3B3 and MCM7 leads to an increase of cell death of both PC3 and DU145 cells. Such cell death induction is partially rescued by expressing spliced c-Met. To our knowledge, this is the first report suggesting that MCM7 is a crit...

We compare the association of an ortho-substituted and a planar PCB (polychlorinated biphenyls PC... more We compare the association of an ortho-substituted and a planar PCB (polychlorinated biphenyls PCB-52 and PCB-77, respectively) with single-component phospholipid bilayers terminated with phosphocholine headgroups. First, fluorescence correlation spectroscopy (FCS) studies of diffusion on supported fluid-phase DLPC show that the ortho-substituted PCB diffuses more slowly, indicating either complex formation or obstructed diffusion. Differential scanning calorimetry (DSC) of vesicles formed from DMPC shows that the gel-tofluid phase transition temperature is lower for vesicles containing this ortho-substituted PCB. Atomic force microscopy (AFM) shows that, whereas supported bilayers of DMPC containing this ortho-substituted PCB display two melting points, bilayers containing the coplanar PCB display just a single melting point. A model is proposed in which the ortho-substituted PCB resides within the lipid tails of these phospholipid bilayers but the coplanar PCB associates preferentially with the headgroups. This model is consistent with the known membrane disruptive ability of the ortho substituted isomer.

Here we introduce a form of chromatography that can be imposed on the membrane of a living cell. ... more Here we introduce a form of chromatography that can be imposed on the membrane of a living cell. A cell-cell signaling interaction is reconstituted in a hybrid live cell-supported membrane junction. The chromatographic material consists of a hexagonally ordered array of gold nanoparticles (nanodot array), which is fabricated onto the underlying substrate. While individual membrane components move freely throughout the array, the movement of larger assemblies is impeded if they exceed the physical dimensions of the array. This tactile approach to probing membrane structures in living cells reveals organizational aspects of the membrane environment unobservable by other techniques.

Janus particles possess functional asymmetry and directionality within a single entity and thus a... more Janus particles possess functional asymmetry and directionality within a single entity and thus are predicted to enable many promising biomedical applications that are not offered by homogeneous particles. However, it remains elusive what role the Janus principle plays in Janus particle-cell interactions, particularly in cellular uptake. We studied how asymmetric distribution of ligands on half-coated Janus microparticles dictates the membrane dynamics during receptor-mediated particle uptake, and found key differences from those characteristic of homogeneous particles. Live-cell fluorescence imaging combined with single-particle level quantification of particle-cell membrane interactions shows that the asymmetric distribution of ligands leads to a three-step endocytic process: membrane cup formation on the ligand-coated hemisphere, stalling at the Janus interface, and rapid membrane protrusion on the ligand-absent hemisphere to complete the particle engulfment. The direct correlation between the spatial presentation of ligands on Janus particles and the temporal changes of membrane dynamics revealed in this work elucidates the potential of using the Janus principle to fine-tune particle-cell interactions.

We show that cationic nanoparticles encapsulated within vesicles of phosphocholine lipid can indu... more We show that cationic nanoparticles encapsulated within vesicles of phosphocholine lipid can induce pearling. The dynamic process occurs as two stages: formation of tubular protrusions followed by pearling instability. The breakup into individual vesicles can be controlled by nanoparticle concentration.

ACS Applied Materials & Interfaces, 2014

Here we show that the multifunctionality of Janus particles can be exploited for in vitro T cell ... more Here we show that the multifunctionality of Janus particles can be exploited for in vitro T cell activation. We engineer bifunctional Janus particles on which the spatial distribution of two ligands, anti-CD3 and fibronectin, mimics the "bull's eye" protein pattern formed in the membrane junction between a T cell and an antigen-presenting cell. Different levels of T cell activation can be achieved by simply switching the spatial distribution of the two ligands on the surfaces of the "bull's eye" particles. We find that the ligand pattern also affects clustering of intracellular proteins. This study demonstrates that anisotropic particles, such as Janus particles, can be developed as artificial antigen-presenting cells for modulating T cell activation.

2009 5th International Conference on Wireless Communications, Networking and Mobile Computing, 2009

The location based services (LBS) are become increasingly important on telecommunication applicat... more The location based services (LBS) are become increasingly important on telecommunication applications. Many LBS methods have been developed. Mobile station location technologies, including cell-identification (CI), enhanced observed time difference (E-OTD), observed timed difference of arrival (OTDOA), and other third Generation (3G) location technologies, are evaluated in the paper. Above of all, the assisted GNSS (A-GNSS) is analyzed to settle for

Lecture Notes in Computer Science, 2006

In contemporary brachytherapy procedures, needle placement at the desired target is challenging d... more In contemporary brachytherapy procedures, needle placement at the desired target is challenging due to a variety of reasons. A robot-assisted brachytherapy system can potentially improve needle placement and seed delivery, resulting in enhanced therapeutic delivery. In this paper we present a 16 DOF (degrees-of-freedom) robotic system (9DOF positioning module and 7DOF surgery module) developed and fabricated for prostate brachytherapy. Strategies to reduce needle deflection and target movement were incorporated after extensive experimental validation. Provisions for needle motion and force feedback were included into the system for improving robot control and seed delivery. Preliminary experimental results reveal that the prototype system is sufficiently accurate in placing brachytherapy needles.