Di Chen

Publications (42)133.06 Total impact

• Article: Selective synthesis of Sb₂S₃ nanoneedles and nanoflowers for high performance rigid and flexible photodetectors.

  Junfeng Chao, Bo Liang, Xiaojuan Hou, Zhe Liu, Zhong Xie, Bin Liu, Weifeng Song, Gui Chen, Di Chen, Guozhen Shen
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  ABSTRACT: Needle-like and flower-like antimony sulfide nanostructures were synthesized and applied for both rigid and flexible photodetectors. Rigid photodetectors based on both nanostructures have the features of linear photocurrent characteristics, low linear dynamic range and good sensitivity to light intensity. Especially, the rigid Sb₂S₃ nanoflowers photodetector has high photoresponse characteristics and its response time and decay time were found to be relatively fast as 6 ms and 10 ms respectively. The flexible Sb₂S₃ nanoflowers photodetector has high flexible, light-weight and adequate bendability with a response time of about 0.09 s and recovery time of 0.27 s. Our results revealed that the rigid and flexible photodetectors based on Sb₂S₃ nanostructures have great potential in next generation optoelectronic devices.
  Optics Express 06/2013; 21(11):13639-47. · 3.59 Impact Factor
• Article: Protection of renal function by perfusing donor organs with siRNA in kidney transplantation

  Ph.D Xiufen Zheng, Xusheng Zhang, Hong Ling, Nathan J Johnston, Di Chen, Liangyi Zhou, Leo Siu, Patrick Luke, Anthony M Jevnikar, Weiping Min
  PLoS ONE 05/2013; · 4.09 Impact Factor
• Article: Lactoferricin Enhances BMP7-Stimulated Anabolic Pathways in Intervertebral Disc Cells.

  Michael B Ellman, Jaesung Kim, Howard S An, Di Chen, Ranjan Kc, Xin Li, Guozhi Xiao, Dongyao Yan, Joon Suh, Andre J van Wjnen, James H-C Wang, Su-Gwan Kim, Hee-Jeong Im
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  ABSTRACT: Bone-morphogenetic protein-7 (BMP7) is a well-known anabolic and anti-catabolic growth factor on intervertebral disc (IVD) matrix and cell homeostasis. Similarly, Lactoferricin B (LfcinB) has recently been shown to have pro-anabolic, anti-catabolic, anti-oxidative and/or anti-inflammatory effects in bovine disc cells in vitro. In this study, we investigated the potential benefits of using combined peptide therapy with LfcinB and BMP7 for intervertebral disc matrix repair and to understand cellular and signaling mechanisms controlled by these factors. We studied the effects of BMP7 and LfcinB as individual treatments and combined therapy on bovine nucleus pulposus (NP) cells by assessing proteoglycan (PG) accumulation and synthesis, and the gene expression of matrix protein aggrecan and transcription factor SOX-9. We also analyzed the role of Noggin, a BMP antagonist, in IVD tissue and examined its effect after stimulation with LfcinB. To understand the molecular mechanisms by which LfcinB synergizes with BMP7, we investigated the ERK-SP1 axis as a downstream intracellular signaling regulator involved in BMP7 and LfcinB-mediated activities. Treatment of bovine NP cells cultured in alginate with LfcinB plus BMP7 synergistically stimulates PG synthesis and accumulation in part by upregulation of aggrecan gene expression. The synergism results from LfcinB-mediated activation of Sp1 and SMAD signaling pathways by (i) phosphorylation of SMAD 1/5/8; (ii) downregulation of SMAD inhibitory factors [i.e., noggin and SMAD6 (inhibitory SMAD)]; and (iii) upregulation of SMAD4 (universal co-SMAD). These data indicate that LfcinB-suppression of Noggin may eliminate the negative feedback of BMP7, thereby maximizing biological activity of BMP7 and ultimately shifting homeostasis to a pro-anabolic state in disc cells. We propose that combination growth factor therapy using BMP7 and LfcinB may be beneficial for treatment of disc degeneration.
  Gene 04/2013; · 2.34 Impact Factor
• Article: Fabrication of high-quality ZnTe nanowires toward high-performance rigid/flexible visible-light photodetectors.

  Zhe Liu, Gui Chen, Bo Liang, Gang Yu, Hongtao Huang, Di Chen, Guozhen Shen
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  ABSTRACT: ZnTe is an important p-type semiconductor with great applications as field-effect transistors and photodetectors. In this paper, individual ZnTe nanowires based field-effect transistors was fabricated, showing evident p-type conductivity with an effect mobility of 11.3 cm²/Vs. Single ZnTe nanowire based photodetectors on rigid silicon substrate exhibited high sensitivity and excellent stability to visible incident light with responstivity and quantum efficiency as high as 1.87 × 10⁵ A/W and 4.36 × 10⁷% respectively and are stable in a wide temperature range (25-250 °C). The polarization-sensitivity of the ZnTe nanowires was studied for the first time. The results revealed a periodic oscillation with the continuous variation of polarization angles. Besides, flexible photodetectors were also fabricated with the features of excellent flexibility, stability and sensitivity to visible incident light. Our work would enable application opportunities in using ZnTe nanowires for ultrahigh-performance photodetectors in scientific, commercial and industrial applications.
  Optics Express 03/2013; 21(6):7799-810. · 3.59 Impact Factor
• Article: Lactoferricin mediates anti-inflammatory and anti-catabolic effects via inhibition of IL-1 and LPS activity in the intervertebral disc.

  Jae-Sung Kim, Michael B Ellman, Dongyao Yan, Howard S An, Ranjan Kc, Xin Li, Di Chen, Guozhi Xiao, Gabriella Cs-Zabo, David W Hoskin, D D Buechter, Andre J van Wijnen, Hee-Jeong Im
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  ABSTRACT: The catabolic cytokine interleukin-1 (IL-1) and endotoxin lipopolysaccharide (LPS) are well-known inflammatory mediators involved in degenerative disc disease, and inhibitors of IL-1 and LPS may potentially be used to slow or prevent disc degeneration in vivo. Here, we elucidate the striking anti-catabolic and anti-inflammatory effects of bovine lactoferricin (LfcinB) in the intervertebral disc (IVD) via antagonism of both IL-1 and LPS-mediated catabolic activity using in vitro and ex vivo analyses. Specifically, we demonstrate the biological counteraction of LfcinB against IL-1 and LPS-mediated proteoglycan (PG) depletion, matrix-degrading enzyme production and enzyme activity in long-term (alginate beads) and short-term (monolayer) culture models using bovine and human nucleus pulposus (NP) cells. LfcinB significantly attenuates the IL-1 and LPS-mediated suppression of PG production and synthesis, and thus restores PG accumulation and pericellular matrix formation. Simultaneously, LfcinB antagonizes catabolic factor mediated induction of multiple cartilage-degrading enzymes, including MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5, in bovine NP cells at both mRNA and protein levels. LfcinB also suppresses the catabolic factor-induced stimulation of oxidative and inflammatory factors such as iNOS, IL-6, and toll-like receptor-2 (TLR-2) and TLR-4. Finally, the ability of LfcinB to antagonize IL-1 and LPS-mediated suppression of PG is upheld in an en bloc intradiscal microinjection model followed by ex vivo organ culture using both mouse and rabbit IVD tissue, suggesting a potential therapeutic benefit of LfcinB on degenerative disc disease in the future. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc.
  Journal of Cellular Physiology 03/2013; · 3.87 Impact Factor
• Article: Contact printing of horizontally-aligned p-type Zn(3)P(2) nanowire arrays for rigid and flexible photodetectors.

  Gang Yu, Bo Liang, Hongtao Huang, Gui Chen, Zhe Liu, Di Chen, Guozhen Shen
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  ABSTRACT: Zn(3)P(2) is an important p-type semiconductor with the ability to detect almost all visible and ultraviolet light. By using the simple and efficient contact printing process, we reported the assembly of horizontally-aligned p-type Zn(3)P(2) nanowire arrays to be used as building blocks for high performance photodetectors. Horizontally-aligned Zn(3)P(2) nanowire arrays were first printed on silicon substrate to make thin-film transistors, exhibiting typical p-type transistor behavior with a high on/off ratio of 10(3). Besides, the Zn(3)P(2) nanowire array based devices showed a substantial response to illuminated lights with a wide range of wavelengths and densities. Flexible photodetectors were also fabricated by contact printing of horizontally-aligned Zn(3)P(2) nanowire arrays on flexible PET substrate, showing a comparable performance to the device on rigid silicon substrate.
  Nanotechnology 02/2013; 24(9):095703. · 3.98 Impact Factor
• Article: Bovine lactoferricin induces TIMP-3 via the ERK1/2-Sp1 axis in human articular chondrocytes.

  Dongyao Yan, Di Chen, John R Hawse, Andre J van Wijnen, Hee-Jeong Im
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  ABSTRACT: Bovine lactoferricin (LfcinB) is a heparan sulfate-binding peptide with multiple bioactivities. In human articular cartilage, LfcinB antagonizes interleukin-1 β (IL-1β) and fibroblast growth factor 2 (FGF-2) in proteoglycan metabolism, catabolic protease expression, and induction of pro-inflammatory mediators. LfcinB specifically activates ERK1/2, p38 and Akt, but whether these signaling pathways control the expression of LfcinB target genes remained unknown. In this report, we characterized a novel aspect of LfcinB-mediated genetic response in human articular chondrocytes, tissue inhibitor of metalloproteinase 3 (TIMP-3) induction. Inhibition of individual signaling pathways revealed that ERK1/2 functions as the major pathway in TIMP-3 expression, whereas Akt plays a minor role. Further investigation identified Sp1 as a critical transcriptional activator in TIMP-3 regulation, and Sp1 activity is modulated by ERK1/2, not Akt. Comparative quantification indicates significant downregulation of TIMP-3 occurs in OA chondrocytes, suggesting a beneficial role of LfcinB in OA pathogenesis. Our results collectively provide new insights into the mechanism of action of LfcinB, and support the candidacy of LfcinB as a chondroprotective agent.
  Gene 01/2013; · 2.34 Impact Factor
• Article: Silencing IDO in dendritic cells: A novel approach to enhance cancer immunotherapy in a murine breast cancer model.

  Xiufen Zheng, James Koropatnick, Di Chen, Thomas Velenosi, Hong Ling, Xusheng Zhang, Nan Jiang, Benjamin Navarro, Thomas E Ichim, Bradley Urquhart, Wei-Ping Min
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  ABSTRACT: Cancer immunotherapeutic agents (vaccines) in the form of antigen-loaded dendritic cells (DCs) reached an important milestone with the recent approval of Provenge, the first DC vaccine for treatment of prostate cancer. Although this heralds a new era of tumor immunotherapy, it also highlights the compelling need to optimize such DC-based therapies as they are increasingly tested and used to treat human patients. In this study we sought to augment and enhance the anti-tumor activity of a DC-based vaccine using siRNA to silence expression of immunosuppressive enzyme indoleamine 2, 3-dioxygenase (IDO) in DCs. We report here that DCs loaded with tumor antigens, but with siRNA-silenced IDO expression, were introduced into 4T1 breast tumor-bearing mice, the treatment: i) lengthened the time required for tumor onset, ii) decreased tumor size compared to tumors grown for equal lengths of time in mice treated with antigen-loaded DCs without IDO silencing, and iii) reduced CD4(+) and CD8(+) T cell apoptosis. Furthermore, immunization with IDO-silenced DCs enhanced tumor antigen-specific T cell proliferation and CTL activity, and decreased numbers of CD4(+) CD25(+) Foxp3(+) T(reg) . This study provides evidence to support silencing of immunosuppressive genes (IDO) as an effective strategy to enhance the efficacy of DC-based cancer immunotherapeutic.
  International Journal of Cancer 07/2012; · 5.44 Impact Factor
• Article: Bovine lactoferricin, an antimicrobial peptide, is anti-inflammatory and anti-catabolic in human articular cartilage and synovium.

  Dongyao Yan, Di Chen, Jie Shen, Guozhi Xiao, Andre J van Wijnen, Hee-Jeong Im
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  ABSTRACT: Bovine lactoferricin (LfcinB) is a multi-functional peptide derived from proteolytic cleavage of bovine lactoferrin. LfcinB was found to antagonize the biological effects mediated by angiogenic growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) in endothelial cells. However, the effect of LfcinB on human articular cartilage remained unknown. Here, our findings demonstrate that LfcinB restored the proteoglycan loss promoted by catabolic factors (interleukin-1 β) IL-1β and FGF-2 in vitro and ex vivo. Mechanistically, LfcinB attenuated the effects of IL-1β and FGF-2 on the expression of cartilage-degrading enzymes (MMP-1, MMP-3, and MMP-13), destructive cytokines (IL-1β and IL-6), and inflammatory mediators (iNOS and TLR2). LfcinB induced protective cytokine expression (IL-4 and IL-10), and downregulated aggrecanase basal expression. LfcinB specifically activated ERK MAPK and Akt signaling pathways, which may account for its anti-inflammatory activity. We also revealed that LfcinB exerted similar protective effects on human synovial fibroblasts challenged by IL-1β, with minimal cytotoxicity. Collectively, our results suggest that LfcinB possesses potent anti-catabolic and anti-inflammatory bioactivities in human articular tissues, and may be utilized for the prevention and/or treatment of OA in the future. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.
  Journal of Cellular Physiology 06/2012; · 3.87 Impact Factor
• Source

  Available from: Meina Wang

  Article: Reply.

  Meina Wang, Hee-Jeong Im, Di Chen
  Arthritis & Rheumatism 06/2012; · 7.87 Impact Factor
• Article: Toll-like receptor adaptor signaling molecule MyD88 on intervertebral disk homeostasis: in vitro, ex vivo studies.

  Michael B Ellman, Jae-Sung Kim, Howard S An, Di Chen, Ranjan KC, Jennifer An, Teju Dittakavi, Andre J van Wijnen, Gabriella Cs-Szabo, Xin Li, Guozhi Xiao, Steven An, Su-Gwan Kim, Hee-Jeong Im
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  ABSTRACT: MyD88 is an adapter protein that links toll-like receptors (TLRs) and Interleukin-1 receptors (IL-1Rs) with downstream signaling molecules. The MyD88 has been found to be an essential mediator in the development of osteoarthritis in articular cartilage. However, the role of the MyD88 pathway has yet to be elucidated in the intervertebral disk (IVD). Using in vitro techniques, we analyzed the effect of MyD88 pathway-specific inhibition on the potent inflammatory and catabolic mediator LPS and IL-1 in bovine and human nucleus pulposus (NP) cells by assessing matrix-degrading enzyme expression, including matrix metalloproteases (MMPs) and a disintegrin-like and metalloprotease with thrombospondin motifs (ADAMTS family). We also analyzed inhibition of MyD88 in the regulation of inducible nitric oxide synthase and TLR-2. Finally, we used an ex vivo organ culture model to assess the effects of MyD88 inhibitor (MyD88i) on catabolic factor-induced disk degeneration in mice lumbar disks. In bovine NP cells, MyD88i potently antagonizes LPS- or IL-1-mediated induction of cartilage-degrading enzyme production, including MMP-1, MMP-13, ADAMTS-4, and ADAMTS-5. MyD88i also attenuates the LPS- or IL-1-mediated induction of iNOS and TLR-2 gene expression. Our ex vivo findings reveal inhibition of MyD88 via counteraction of IL-1-mediated proteoglycan depletion. The findings from this study demonstrate the potent anti-inflammatory and anti-catabolic effects of inhibition of MyD88 pathway inhibition on IVD homeostasis, suggesting a potential therapeutic benefit of a MyD88i in degenerative disk disease in the future.
  Gene 06/2012; 505(2):283-90. · 2.34 Impact Factor
• Article: Transparent metal oxide nanowire transistors.

  Di Chen, Zhe Liu, Bo Liang, Xianfu Wang, Guozhen Shen
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  ABSTRACT: With the features of high mobility, a high electric on/off ratio and excellent transparency, metal oxide nanowires are excellent candidates for transparent thin-film transistors, which is one of the key technologies to realize transparent electronics. This article provides a comprehensive review of the state-of-the-art research activities that focus on transparent metal oxide nanowire transistors. It begins with the brief introduction to the synthetic methods for high quality metal oxide nanowires, and the typical nanowire transfer and printing techniques with emphasis on the simple contact printing methodology. High performance transparent transistors built on both single nanowires and nanowire thin films are then highlighted. The final section deals with the applications of transparent metal oxide nanowire transistors in the field of transparent displays and concludes with an outlook on the current perspectives and future directions of transparent metal oxide nanowire transistors.
  Nanoscale 04/2012; 4(10):3001-12. · 5.91 Impact Factor
• Article: Association of metals and proteasome activity in erythrocytes of prostate cancer patients and controls.

  Christine Neslund-Dudas, Bharati Mitra, Ashoka Kandegedara, Di Chen, Sara Schmitt, Min Shen, Qiuzhi Cui, Benjamin A Rybicki, Q Ping Dou
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  ABSTRACT: Information is lacking on the effects toxic environmental metals may have on the 26S proteasome. The proteasome is a primary vehicle for selective degradation of damaged proteins in a cell and due to its role in cell proliferation, inhibition of the proteasome has become a target for cancer therapy. Metals are essential to the proteasome's normal function and have been used within proteasome-inhibiting complexes for cancer therapy. This study evaluated the association of erythrocyte metal levels and proteasome chymotrypsin-like (CT-like) activity in age- and race-matched prostate cancer cases (n = 61) and controls (n = 61). Erythrocyte metals were measured by inductively coupled plasma mass spectrometry (ICP-MS). CT-like activity was measured by proteasome activity assay using a fluorogenic peptide substrate. Among cases, significant correlations between individual toxic metals were observed (r(arsenic-cadmium) = 0.49, p < 0.001; r(arsenic-lead) = 0.26, p = 0.04, r(cadmium-lead) 0.53, p < 0.001), but there were no significant associations between metals and CT-like activity. In contrast, within controls there were no significant associations between metals, however, copper and lead levels were significantly associated with CT-like activity. The associations between copper and lead and proteasome activity (r(copper-CT-like) = -0.28, p = 0.002 ; r(lead-CT-like) = 0.23, p = 0.011) remained significant in multivariable models that included all of the metals. These findings suggest that biologically essential metals and toxic metals may affect proteasome activity in healthy controls and, further, show that prostate cancer cases and controls differ in associations between metals and proteasome activity in erythrocytes. More research on toxic metals and the proteasome in prostate cancer is warranted.
  Biological trace element research 03/2012; 149(1):5-9. · 1.92 Impact Factor
• Source

  Available from: Meina Wang

  Article: Conditional activation of β-catenin signaling in mice leads to severe defects in intervertebral disc tissue.

  Meina Wang, Dezhi Tang, Bing Shu, Baoli Wang, Hongting Jin, Suyang Hao, Karen A Dresser, Jie Shen, Hee-Jeong Im, Erik R Sampson, Paul T Rubery, Michael J Zuscik, Edward M Schwarz, Regis J O'Keefe, Yongjun Wang, Di Chen
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  ABSTRACT: The incidence of low back pain is extremely high and is often linked to intervertebral disc (IVD) degeneration. The mechanism of this disease is currently unknown. This study was undertaken to investigate the role of β-catenin signaling in IVD tissue function. β-catenin protein levels were measured by immunohistochemical analysis of disc samples obtained from patients with disc degeneration and from normal subjects. To generate β-catenin conditional activation (cAct) mice, Col2a1-CreER(T2) -transgenic mice were bred with β-catenin(fx(Ex3)/fx(Ex3)) mice. Changes in disc tissue morphology and function were examined by micro-computed tomography, histologic analysis, and real-time polymerase chain reaction assays. β-catenin protein was up-regulated in disc tissue samples from patients with disc degeneration. To assess the effects of increased β-catenin levels on disc tissue, we generated β-catenin cAct mice. Overexpression of β-catenin in disc cells led to extensive osteophyte formation in 3- and 6-month-old β-catenin cAct mice, which were associated with significant changes in the cells and extracellular matrix of disc tissue and growth plate. Gene expression analysis demonstrated that activation of β-catenin enhanced runt-related transcription factor 2-dependent Mmp13 and Adamts5 expression. Moreover, genetic ablation of Mmp13 or Adamts5 on the β-catenin cAct background, or treatment of β-catenin cAct mice with a specific matrix metalloproteinase 13 inhibitor, ameliorated the mutant phenotype. Our findings indicate that the β-catenin signaling pathway plays a critical role in disc tissue function.
  Arthritis & Rheumatism 03/2012; 64(8):2611-23. · 7.87 Impact Factor
• Article: Species-specific biological effects of FGF-2 in articular cartilage: implication for distinct roles within the FGF receptor family.

  Xin Li, Michael B Ellman, Jeffrey S Kroin, Di Chen, Dongyao Yan, Katalin Mikecz, Ranjan K C, Guozhi Xiao, Gary S Stein, Su-Gwan Kim, Brian Cole, Andre J van Wijnen, Hee-Jeong Im
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  ABSTRACT: Existing literature demonstrates that fibroblast growth factor-2 (FGF-2) exerts opposing, contradictory biological effects on cartilage homeostasis in different species. In human articular cartilage, FGF-2 plays a catabolic and anti-anabolic role in cartilage homeostasis, driving homeostasis toward degeneration and osteoarthritis (OA). In murine joints, however, FGF-2 has been identified as an anabolic mediator as ablation of the FGF-2 gene demonstrated increased susceptibility to OA. There have been no previous studies specifically addressing species-specific differences in FGF-2-mediated biological effects. In this study, we provide a mechanistic understanding by which FGF-2 exerts contradictory biological effects in human versus murine tissues. Using human articular cartilage (ex vivo) and a medial meniscal destabilization (DMM) animal model (in vivo), species-specific expression patterns of FGFR receptors (FGFRs) are elucidated between human and murine articular cartilage. In the murine OA model followed by intra-articular injection of FGF-2, we further correlate FGFR profiles to changes in behavioral pain perception, proteoglycan content in articular cartilage, and production of inflammatory (CD11b) and angiogenic (VEGF) mediators in synovium lining cells. Our results suggest that the fundamental differences in cellular responses between human and murine tissues may be secondary to distinctive expression patterns of FGFRs that eventually determine biological outcomes in the presence of FGF-2. The complex interplay of FGFRs and the downstream signaling cascades induced by FGF-2 in human cartilage should add caution to the use of this particular growth factor for biological therapy in the future.
  Journal of Cellular Biochemistry 03/2012; 113(7):2532-42. · 2.87 Impact Factor
• Article: Needle-like Zn-doped SnO2 nanorods with enhanced photocatalytic and gas sensing properties.

  Hongtao Huang, Shouqin Tian, Jing Xu, Zhong Xie, Dawen Zeng, Di Chen, Guozhen Shen
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  ABSTRACT: Zn-doped SnO(2) nanorods have been prepared by a simple hydrothermal method on a large scale. The as-prepared samples were characterized by x-ray powder diffraction, scanning electron microscope, transmission electron microscope, energy dispersive spectrometer, x-ray photoelectron spectroscopy, UV-vis absorption spectra and photoluminescence spectra. Studies found that the products are needle-like single-crystalline nanorods grown along the [[Formula: see text]] orientation. The photocatalytic properties of the synthesized Zn-doped SnO(2) were investigated by decomposing acid fuchsine, showing much higher photocatalytic activity than pure SnO(2) nanorods and bulk SnO(2) powders. An enhanced gas sensing ability toward methanal, ethanol and acetone gases is also achieved in high sensitivity and fast response. The origins of the enhanced performances are discussed.
  Nanotechnology 02/2012; 23(10):105502. · 3.98 Impact Factor
• Article: S-Nitrosated human serum albumin dimer is not only a novel anti-tumor drug but also a potentiator for anti-tumor drugs with augmented EPR effects.

  Yu Ishima, Di Chen, Jun Fang, Hiroshi Maeda, Ai Minomo, Ulrich Kragh-Hansen, Toshiya Kai, Toru Maruyama, Masaki Otagiri
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  ABSTRACT: Macromolecules have been developed as carriers of low-molecular-weight drugs in drug delivery systems (DDS) to improve their pharmacokinetic profile or to promote their uptake in tumor tissue via enhanced permeability and retention (EPR) effects. In the present study, recombinant human serum albumin dimer (AL-Dimer), which was designed by linking two human serum albumin (HSA) molecules with the amino acid linker (GGGGS)(2), significantly accumulated in tumor tissue even more than HSA Monomer (AL-Monomer) and appearing to have good retention in circulating blood in murine colon 26 (C26) tumor-bearing mice. Moreover, we developed S-nitrosated AL-Dimer (SNO-AL-Dimer) as a novel DDS compound containing AL-Dimer as a carrier, and nitric oxide (NO) as (i) an anticancer therapeutic drug/cell death inducer and (ii) an enhancer of the EPR effect. We observed that SNO-AL-Dimer treatment induced apoptosis of C26 tumor cells in vitro, depending on the concentration of NO. In in vivo experiments, SNO-AL-Dimer was found to specifically deliver large amounts of cytotoxic NO into tumor tissue but not into normal organs in C26 tumor-bearing mice as compared with control (untreated tumor-bearing mice) and SNO-AL-Monomer-treated mice. Intriguingly, S-nitrosation improved the uptake of AL-Dimer in tumor tissue through augmenting the EPR effect. These data suggest that SNO-AL-Dimer behaves not only as an anticancer therapeutic drug, but also as a potentiator of the EPR effect. Therefore, SNO-AL-Dimer would be a very appealing carrier for utilization of the EPR effect in future development of cancer therapeutics.
  Bioconjugate Chemistry 02/2012; 23(2):264-71. · 4.93 Impact Factor
• Article: Zn2GeO4 and In2Ge2O7 nanowire mats based ultraviolet photodetectors on rigid and flexible substrates.

  Zhe Liu, Hongtao Huang, Bo Liang, Xianfu Wang, Zhuoran Wang, Di Chen, Guozhen Shen
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  ABSTRACT: Ternary metal oxide, Zn2GeO4, In2Ge2O7, have potential applications in many research areas. Using a single chemical vapor deposition method, high-quality single crystalline Zn2GeO4 nanowire (NW) mats and In2Ge2O7 NW mats were synthesized on a large scale. Nanowires mats based ultraviolet photodetectors were fabricated on rigid silicon substrates. By simply transferring the nanowire mats to a transparent adhesive PET tape, flexible photodetectors were also fabricated. Both the rigid and flexible photodetectors exhibited excellent photoconductive performance in terms of high sensitivity to the UV light, excellent stability and reproducibility, and fast response and recovery time.
  Optics Express 01/2012; 20(3):2982-91. · 3.59 Impact Factor
• Article: Sequential delivery of BMP-2 and IGF-1 using a chitosan gel with gelatin microspheres enhances early osteoblastic differentiation.

  Sungwoo Kim, Yunqing Kang, Chad A Krueger, Milan Sen, John B Holcomb, Di Chen, Joseph C Wenke, Yunzhi Yang
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  ABSTRACT: The purpose of this study was to develop and characterize a chitosan gel/gelatin microsphere (MSs) dual delivery system for sequential release of bone morphogenetic protein-2 (BMP-2) and insulin-like growth factor-1 (IGF-1) to enhance osteoblast differentiation in vitro. We made and characterized the delivery system based on its degree of cross-linking, degradation, and release kinetics. We also evaluated the cytotoxicity of the delivery system and the effect of growth factors on cell response using pre-osteoblast W-20-17 mouse bone marrow stromal cells. IGF-1 was first loaded into MSs, and then the IGF-1-containing MSs were encapsulated into the chitosan gel which contained BMP-2. Cross-linking of gelatin with glyoxal via Schiff bases significantly increased thermal stability and decreased the solubility of the MSs, leading to a significant decrease in the initial release of IGF-1. Encapsulation of the MSs into the chitosan gel generated polyelectrolyte complexes by intermolecular interactions, which further affected the release kinetics of IGF-1. This combinational delivery system provided an initial release of BMP-2 followed by a slow and sustained release of IGF-1. Significantly greater alkaline phosphatase activity was found in W-20-17 cells treated with the sequential delivery system compared with other treatments (P<0.05) after a week of culture.
  Acta biomaterialia 01/2012; 8(5):1768-77. · 3.98 Impact Factor
• Article: Biological effects of the plant-derived polyphenol resveratrol in human articular cartilage and chondrosarcoma cells.

  Hee-Jeong Im, Xin Li, Di Chen, Dongyao Yan, Jaesung Kim, Michael B Ellman, Gary S Stein, Brian Cole, Ranjan Kc, Gabriella Cs-Szabo, Andre J van Wijnen
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  ABSTRACT: The natural phytoestrogen resveratrol (RSV) may have therapeutic potential for arthritic conditions. RSV is chondroprotective for articular cartilage in rabbit models for arthritis, but its biological effects on human articular cartilage and chondrosarcoma cells are unknown. Effects of RSV on human articular cartilage homeostasis were studied by assessing production of matrix-degrading enzymes (MMP-13, ADAMTS4, and ADAMTS5), as well as proteoglycan production and synthesis. The counteractions of RSV against catabolic factors (e.g., FGF-2 or IL-1β) were examined by in vitro and ex vivo using monolayer, three-dimensional alginate beads and cartilage explants cultures, respectively. RSV improves cell viability of articular chondrocytes and effectively antagonizes cartilage-degrading protease production that was initiated by catabolic and/or anti-anabolic cytokines in human articular chondrocytes. RSV significantly also enhances BMP7-promoted proteoglycan synthesis as assessed by (35) S-sulfate incorporation. Protein-DNA interaction arrays suggest that RSV inhibits the activation of transcription factors involved in inflammation and cartilage catabolic signaling pathways, including direct downstream regulators of MAPK (e.g., AP-1, PEA3) and NFκB. RSV selectively compromises survival of human chondrosarcoma cells, but not primary articular chondrocytes, revealing cell-specific activity of RSV on non-tumorigenic versus tumor-derived cells. We propose that RSV exerts its chondroprotective functions, in part, by deactivating p53-induced apoptosis in human primary chondrocytes, but not human chondrosarcoma. Our findings suggest that RSV has potential as a unique biologic treatment for both prevention and treatment of cartilage degenerative diseases.
  Journal of Cellular Physiology 01/2012; 227(10):3488-97. · 3.87 Impact Factor