Hsin-Hou Chang | Tzu Chi University (original) (raw)

Papers by Hsin-Hou Chang

Research paper thumbnail of Megakaryocytic differentiation of mouse embryonic stem cells via coculture with immortalized OP9 stromal cells

Experimental cell research, Jan 7, 2015

Established from the calvaria of newborn macrophage colony-stimulating factor (M-CSF)-deficient m... more Established from the calvaria of newborn macrophage colony-stimulating factor (M-CSF)-deficient mice, OP9 is a stromal cell line that used as a feeder layer to support the in vitro differentiation of pluripotent stem cells into various hematopoietic lineage cells, including granulocytes, erythrocytes, lymphocytes, and megakaryocytes. However, as a primary culture cell line, OP9 can be used as stromal cells for only 1 month. Therefore, to obtain functional OP9 cells, numerous M-CSF-deficient newborn mice must be sacrificed. These limitations in some ways restrict the application of OP9 cells in longterm and largescale experiments. In this study, we used human papillomavirus 16 E6 and E7 genes to generate immortalized OP9 stromal cells, designated I-OP9 cells, and then tested their ability to support the megakaryocytic differentiation of pluripotent stem cells in vitro. I-OP9 cells have similar morphology and properties as do parental OP9 cells, and, as expected, have an extended life...

Research paper thumbnail of Endothelial Cell Sensitization by Death Receptor Fractions of an Anti-Dengue Nonstructural Protein 1 Antibody Induced Plasma Leakage, Coagulopathy, and Mortality in Mice

Journal of immunology (Baltimore, Md. : 1950), Jan 15, 2015

The mechanisms leading to the life-threatening dengue hemorrhagic fever (DHF) remain elusive. DHF... more The mechanisms leading to the life-threatening dengue hemorrhagic fever (DHF) remain elusive. DHF preferentially occurs during secondary dengue infections, suggesting that aberrant immune responses are involved in its development. We previously demonstrated that the autoantibodies elicited by dengue virus (DENV) nonstructural protein 1 (NS1; anti-NS1 Igs) induce plasma leakage and mortality in mice with warfarinized anticoagulant suppression. However, the involved pathogenic Ig fractions of anti-NS1 Igs remain unclear. In this study, the autoreactive Igs in patients with DHF and in NS1-immunized rabbits crossreacted with TNF-related apoptosis-inducing ligand receptor 1 (death receptor [DR]4). Challenges with the DENV in a subcytotoxic dose sensitized endothelial cells to apoptosis. Treatments with the autoantibodies induced proapoptotic activities and suppressed the surface expression of endothelial anticoagulant thrombomodulin. Combined treatments comprising the DENV and DR4 affini...

Research paper thumbnail of Antibacterial property of Ag nanoparticle-impregnated N-doped titania films under visible light

Scientific Reports, 2015

Photocatalysts produce free radicals upon receiving light energy; thus, they possess antibacteria... more Photocatalysts produce free radicals upon receiving light energy; thus, they possess antibacterial properties. Silver (Ag) is an antibacterial material that disrupts bacterial physiology. Our previous study reported that the high antibacterial property of silver nanoparticles on the surfaces of visible light-responsive nitrogen-doped TiO 2 photocatalysts [TiO 2 (N)] could be further enhanced by visible light illumination. However, the major limitation of this Ag-TiO 2 composite material is its durability; the antibacterial property decreased markedly after repeated use. To overcome this limitation, we developed TiO 2 (N)/Ag/TiO 2 (N) sandwich films in which the silver is embedded between two TiO 2 (N) layers. Various characteristics, including silver and nitrogen amounts, were examined in the composite materials. Various analyses, including electron microscopy, energy dispersive spectroscopy, X-ray diffraction, and ultraviolet-visible absorption spectrum and methylene blue degradation rate analyses, were performed. The antibacterial properties of the composite materials were investigated. Here we revealed that the antibacterial durability of these thin films is substantially improved in both the dark and visible light, by which bacteria, such as Escherichia coli, Streptococcus pyogenes, Staphylococcus aureus, and Acinetobacter baumannii, could be efficiently eliminated. This study demonstrated a feasible approach to improve the visible-light responsiveness and durability of antibacterial materials that contain silver nanoparticles impregnated in TiO 2 (N) films.

Research paper thumbnail of The Interaction of Protein-Modified Nanodiamond with Bacterial Cells

The nanometer-sized diamond functionalizing and optimization of this process are studied. To crea... more The nanometer-sized diamond functionalizing and optimization of this process are studied. To create the functional groups on the nanodiamond surface the carboxylation/oxidization of 100 nm nanodiamonds was applied and its IR spectra were analyzed. The surface functionalizing was followed by conjugating with protein (lysozyme) via physical adsorption. Nanodiamond-protein interaction was analyzed using FTIR spectroscopy. The interaction of lysozyme-nanodiamond conjugates with E. Coli bacteria was observed by analyzing the adsorbed lysozyme antibacterial activity. Nanodiamond-lysozyme conjugates displayed high activity, equivalent to activity of lysozyme in solution. The results demonstrated that the lysozyme preserved its functionality in conjugates with nanodiamond, while in the same time nanodiamonds can serve as probe using spectroscopic methods.

Research paper thumbnail of Nanodiamonds protect skin from ultraviolet B-induced damage in mice

Journal of nanobiotechnology, 2015

Solar ultraviolet (UV) radiation causes various deleterious effects, and UV blockage is recommend... more Solar ultraviolet (UV) radiation causes various deleterious effects, and UV blockage is recommended for avoiding sunburn. Nanosized titanium dioxide and zinc oxide offer effective protection and enhance cosmetic appearance but entail health concerns regarding their photocatalytic activity, which generates reactive oxygen species. These concerns are absent in nanodiamonds (NDs). Among the UV wavelengths in sunlight, UVB irradiation primarily threatens human health. The efficacy and safety of NDs in UVB protection were evaluated using cell cultures and mouse models. We determined that 2 mg/cm(2) of NDs efficiently reduced over 95% of UVB radiation. Direct UVB exposure caused cell death of cultured keratinocyte, fibroblasts and skin damage in mice. By contrast, ND-shielding significantly protected the aforementioned pathogenic alterations in both cell cultures and mouse models. NDs are feasible and safe materials for preventing UVB-induced skin damage.

Research paper thumbnail of Acquired coagulant factor VIII deficiency induced by Bacillus anthracis lethal toxin in mice

Virulence, Jan 23, 2015

Mice treated with anthrax lethal toxin (LT) exhibit hemorrhage caused by unknown mechanisms. More... more Mice treated with anthrax lethal toxin (LT) exhibit hemorrhage caused by unknown mechanisms. Moreover, LT treatment in mice induced liver damage. In this study, we hypothesized that a suppressed coagulation function may be associated with liver damage, because the liver is the major producing source of coagulation factors. The hepatic expression of coagulant factors and the survival rates were analyzed after cultured cells or mice were exposed to LT. In agreement with our hypothesis, LT induces cytotoxicity against hepatic cells in vitro. In addition, suppressed expression of coagulation factor VIII (FVIII) in the liver is associated with a prolonged plasma clotting time in LT-treated mice, suggesting a suppressive role of LT in coagulation. Accordingly, we further hypothesized that a loss-of-function approach involving treatments of an anticoagulant should exacerbate LT-induced abnormalities, whereas a gain-of-function approach involving injections of recombinant FVIII to complemen...

Research paper thumbnail of Differential regulation of caspase-2 in MPP(+)-induced apoptosis in primary cortical neurons

Experimental cell research, 2015

Parkinson׳s disease (PD), among the most common neurodegenerative diseases worldwide for which th... more Parkinson׳s disease (PD), among the most common neurodegenerative diseases worldwide for which there is no cure, is characterized as progressive dopaminergic neuron loss in the substantia nigra through an unknown mechanism. Administering 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) causes neuronal cell death and Parkinsonism in humans. Commonly used in animal models of PD, MPTP can metabolize to 1-methyl-4-phenylpyridinium (MPP(+)); however, the detailed mechanism through which MPP(+) causes neuronal cell death remains undetermined. Previous reports have indicated those knockout mice with Bcl-2 associated protein X (Bax) or caspase-2, two mitochondrial outer membrane permeabilization inducers, are resistant to MPTP administration, suggesting that mitochondria are involved in MPP(+)-triggered apoptosis. Our previous study showed that MPP(+)-triggered apoptosis can be distinguished from spontaneous apoptosis of primary cortical neurons. In the present study, we verified the ...

Research paper thumbnail of Erythrocytic Mobilization Enhanced by the Granulocyte Colony-Stimulating Factor Is Associated with Reduced Anthrax-Lethal-Toxin-Induced Mortality in Mice

PLoS ONE, 2014

Anthrax lethal toxin (LT), one of the primary virulence factors of Bacillus anthracis, causes ant... more Anthrax lethal toxin (LT), one of the primary virulence factors of Bacillus anthracis, causes anthrax-like symptoms and death in animals. Experiments have indicated that levels of erythrocytopenia and hypoxic stress are associated with disease severity after administering LT. In this study, the granulocyte colony-stimulating factor (G-CSF) was used as a therapeutic agent to ameliorate anthrax-LT-and spore-induced mortality in C57BL/6J mice. We demonstrated that G-CSF promoted the mobilization of mature erythrocytes to peripheral blood, resulting in a significantly faster recovery from erythrocytopenia. In addition, combined treatment using G-CSF and erythropoietin tended to ameliorate B. anthracis-spore-elicited mortality in mice. Although specific treatments against LT-mediated pathogenesis remain elusive, these results may be useful in developing feasible strategies to treat anthrax.

Research paper thumbnail of Erythropoiesis Suppression Is Associated with Anthrax Lethal Toxin-Mediated Pathogenic Progression

PLoS ONE, 2013

Anthrax is a disease caused by the bacterium Bacillus anthracis, which results in high mortality ... more Anthrax is a disease caused by the bacterium Bacillus anthracis, which results in high mortality in animals and humans. Although some of the mechanisms are already known such as asphyxia, extensive knowledge of molecular pathogenesis of this disease is deficient and remains to be further investigated. Lethal toxin (LT) is a major virulence factor of B. anthracis and a specific inhibitor/protease of mitogen-activated protein kinase kinases (MAPKKs). Anthrax LT causes lethality and induces certain anthrax-like symptoms, such as anemia and hypoxia, in experimental mice. Mitogen-activated protein kinases (MAPKs) are the downstream pathways of MAPKKs, and are important for erythropoiesis. This prompted us to hypothesize that anemia and hypoxia may in part be exacerbated by erythropoietic dysfunction. As revealed by colony-forming cell assays in this study, LT challenges significantly reduced mouse erythroid progenitor cells. In addition, in a proteolytic activity-dependent manner, LT suppressed cell survival and differentiation of cord blood CD34 + -derived erythroblasts in vitro. Suppression of cell numbers and the percentage of erythroblasts in the bone marrow were detected in LT-challenged C57BL/6J mice. In contrast, erythropoiesis was provoked through treatments of erythropoietin, significantly ameliorating the anemia and reducing the mortality of LT-treated mice. These data suggested that suppressed erythropoiesis is part of the pathophysiology of LT-mediated intoxication. Because specific treatments to overcome LT-mediated pathogenesis are still lacking, these efforts may help the development of effective treatments against anthrax.

Research paper thumbnail of RECOMBINANT SNAKE DISINTEGRINS USED FOR MAMMALIAN INTEGRIN STUDY

Toxin Reviews, 2005

ABSTRACT

Research paper thumbnail of RHODOSTOMIN, A SNAKE VENOM DISINTEGRIN, SERVED AS A MOLECULAR TOOL TO DISSECT THE INTEGRIN FUNCTION

Toxin Reviews, 2007

ABSTRACT

Research paper thumbnail of Correction: The Use of Nanoscale Visible Light-Responsive Photocatalyst TiO 2 -Pt for the Elimination of Soil-Borne Pathogens

PLoS ONE, 2012

Exposure to the soil-borne pathogens Burkholderia pseudomallei and Burkholderia cenocepacia can l... more Exposure to the soil-borne pathogens Burkholderia pseudomallei and Burkholderia cenocepacia can lead to severe infections and even mortality. These pathogens exhibit a high resistance to antibiotic treatments. In addition, no licensed vaccine is currently available. A nanoscale platinum-containing titania photocatalyst (TiO 2 -Pt) has been shown to have a superior visible light-responsive photocatalytic ability to degrade chemical contaminants like nitrogen oxides. The antibacterial activity of the catalyst and its potential use in soil pathogen control were evaluated. Using the plating method, we found that TiO 2 -Pt exerts superior antibacterial performance against Escherichia coli compared to other commercially available and laboratory prepared ultraviolet/visible light-responsive titania photocatalysts. TiO 2 -Pt-mediated photocatalysis also affectively eliminates the soil-borne bacteria B. pseudomallei and B. cenocepacia. An air pouch infection mouse model further revealed that TiO 2 -Pt-mediated photocatalysis could reduce the pathogenicity of both strains of bacteria. Unexpectedly, water containing up to 10% w/v dissolved soil particles did not reduce the antibacterial potency of TiO 2 -Pt, suggesting that the TiO 2 -Pt photocatalyst is suitable for use in soil-contaminated environments. The TiO 2 -Pt photocatalyst exerted superior antibacterial activity against a broad spectrum of human pathogens, including B. pseudomallei and B. cenocepacia. Soil particles (,10% w/v) did not significantly reduce the antibacterial activity of TiO 2 -Pt in water. These findings suggest that the TiO 2 -Pt photocatalyst may have potential applications in the development of bactericides for soilborne pathogens.

Research paper thumbnail of Visible Light Responsive Photocatalyst Induces Progressive and Apical-Terminus Preferential Damages on Escherichia coli Surfaces

PLoS ONE, 2011

Background: Recent research shows that visible-light responsive photocatalysts have potential usa... more Background: Recent research shows that visible-light responsive photocatalysts have potential usage in antimicrobial applications. However, the dynamic changes in the damage to photocatalyzed bacteria remain unclear.

Research paper thumbnail of Suppressive Effects of Anthrax Lethal Toxin on Megakaryopoiesis

PLoS ONE, 2013

Anthrax lethal toxin (LT) is a major virulence factor of Bacillus anthracis. LT challenge suppres... more Anthrax lethal toxin (LT) is a major virulence factor of Bacillus anthracis. LT challenge suppresses platelet counts and platelet function in mice, however, the mechanism responsible for thrombocytopenia remains unclear. LT inhibits cellular mitogenactivated protein kinases (MAPKs), which are vital pathways responsible for cell survival, differentiation, and maturation. One of the MAPKs, the MEK1/2-extracellular signal-regulated kinase pathway, is particularly important in megakaryopoiesis. This study evaluates the hypothesis that LT may suppress the progenitor cells of platelets, thereby inducing thrombocytopenic responses. Using cord blood-derived CD34 + cells and mouse bone marrow mononuclear cells to perform in vitro differentiation, this work shows that LT suppresses megakaryopoiesis by reducing the survival of megakaryocytes. Thrombopoietin treatments can reduce thrombocytopenia, megakaryocytic suppression, and the quick onset of lethality in LT-challenged mice. These results suggest that megakaryocytic suppression is one of the mechanisms by which LT induces thrombocytopenia. These findings may provide new insights for developing feasible approaches against anthrax.

Research paper thumbnail of The Use of Nanoscale Visible Light-Responsive Photocatalyst TiO2-Pt for the Elimination of Soil-Borne Pathogens

PLoS ONE, 2012

Exposure to the soil-borne pathogens Burkholderia pseudomallei and Burkholderia cenocepacia can l... more Exposure to the soil-borne pathogens Burkholderia pseudomallei and Burkholderia cenocepacia can lead to severe infections and even mortality. These pathogens exhibit a high resistance to antibiotic treatments. In addition, no licensed vaccine is currently available. A nanoscale platinum-containing titania photocatalyst (TiO 2 -Pt) has been shown to have a superior visible light-responsive photocatalytic ability to degrade chemical contaminants like nitrogen oxides. The antibacterial activity of the catalyst and its potential use in soil pathogen control were evaluated. Using the plating method, we found that TiO 2 -Pt exerts superior antibacterial performance against Escherichia coli compared to other commercially available and laboratory prepared ultraviolet/visible light-responsive titania photocatalysts. TiO 2 -Pt-mediated photocatalysis also affectively eliminates the soil-borne bacteria B. pseudomallei and B. cenocepacia. An air pouch infection mouse model further revealed that TiO 2 -Pt-mediated photocatalysis could reduce the pathogenicity of both strains of bacteria. Unexpectedly, water containing up to 10% w/v dissolved soil particles did not reduce the antibacterial potency of TiO 2 -Pt, suggesting that the TiO 2 -Pt photocatalyst is suitable for use in soil-contaminated environments. The TiO 2 -Pt photocatalyst exerted superior antibacterial activity against a broad spectrum of human pathogens, including B. pseudomallei and B. cenocepacia. Soil particles (,10% w/v) did not significantly reduce the antibacterial activity of TiO 2 -Pt in water. These findings suggest that the TiO 2 -Pt photocatalyst may have potential applications in the development of bactericides for soilborne pathogens.

Research paper thumbnail of Cell adhesion as a novel approach to determining the cellular binding motif on the severe acute respiratory syndrome coronavirus spike protein

Journal of Virological Methods, 2014

Please cite this article in press as: Chang, H.-H., et al., Cell adhesion as a novel approach to ... more Please cite this article in press as: Chang, H.-H., et al., Cell adhesion as a novel approach to determining the cellular binding motif on the severe acute respiratory syndrome coronavirus spike protein. J. Virol. Methods (2014), http://dx.

Research paper thumbnail of Antiplatelet Activities of Anthrax Lethal Toxin Are Associated with Suppressed p42/44 and p38 Mitogen‐Activated Protein Kinase Pathways in the Platelets

The Journal of Infectious Diseases, 2005

Anthrax lethal toxin (LT) is the major virulence factor produced by Bacillus anthracis, but the m... more Anthrax lethal toxin (LT) is the major virulence factor produced by Bacillus anthracis, but the mechanism by which it induces high mortality remains unclear. We found that LT treatment could induce severe hemorrhage in mice and significantly suppress human whole-blood clotting and platelet aggregation in vitro. In addition, LT could inhibit agonist-induced platelet surface P-selectin expression, resulting in the inhibition of platelet-endothelial cell engagements. Data from Western blot analysis indicated that LT treatment resulted in the suppression of p42/44 and p38 mitogen-activated protein kinase pathways in platelets. Combined treatments with LT and antiplatelet agents such as aspirin and the RGD-containing disintegrin rhodostomin significantly increased mortality in mice. Our data suggest that platelets are a pathogenic target for anthrax LT.

Research paper thumbnail of Facilitation of Cell Adhesion by Immobilized Dengue Viral Nonstructural Protein 1 (NS1): Arginine‐Glycine‐Aspartic Acid Structural Mimicry within the Dengue Viral NS1 Antigen

The Journal of Infectious Diseases, 2002

Dengue virus infection causes life-threatening hemorrhagic fever. Increasing evidence implies tha... more Dengue virus infection causes life-threatening hemorrhagic fever. Increasing evidence implies that dengue viral nonstructural protein 1 (NS1) exhibits a tendency to elicit potentially hazardous autoantibodies, which show a wide spectrum of specificity against extracellular matrix and platelet antigens. How NS1 elicits autoantibodies remains unclear. To address the hypothesis that NS1 and matrix proteins may have structural and functional similarity, cell-matrix and cell-NS1 interactions were evaluated using a cell-adhesion assay. The present study showed that dengue NS1 immobilized on coverslips resulted in more cell adhesion than did the control proteins. This cell adhesion was inhibited by peptides containing arginine-glycine-aspartic acid (RGD), a motif important for integrin-mediated cell adhesion. In addition, anti-NS1 antibodies blocked RGD-mediated cell adhesion. Although there is no RGD motif in the NS1 protein sequence, these data indicate that RGD structural mimicry exists within the NS1 antigen.

Research paper thumbnail of Activated protein C ameliorates Bacillus anthracis lethal toxin-induced lethal pathogenesis in rats

Journal of Biomedical Science, 2012

Background: Lethal toxin (LT) is a major virulence factor of Bacillus anthracis. Sprague Dawley r... more Background: Lethal toxin (LT) is a major virulence factor of Bacillus anthracis. Sprague Dawley rats manifest pronounced lung edema and shock after LT treatments, resulting in high mortality. The heart failure that is induced by LT has been suggested to be a principal mechanism of lung edema and mortality in rodents. Since LT-induced death occurs more rapidly in rats than in mice, suggesting that other mechanisms in addition to the heart dysfunction may be contributed to the fast progression of LT-induced pathogenesis in rats. Coagulopathy may contribute to circulatory failure and lung injury. However, the effect of LT on coagulation-induced lung dysfunction is unclear. Methods: To investigate the involvement of coagulopathy in LT-mediated pathogenesis, the mortality, lung histology and coagulant levels of LT-treated rats were examined. The effects of activated protein C (aPC) on LT-mediated pathogenesis were also evaluated.

Research paper thumbnail of The influence of nanodiamond on the oxygenation states and micro rheological properties of human red blood cells <italic>in vitro</italic>

Journal of Biomedical Optics, 2012

Nanodiamond has been proven to be biocompatible and proposed for various biomedical applications.... more Nanodiamond has been proven to be biocompatible and proposed for various biomedical applications. Recently, nanometer-sized diamonds have been demonstrated as an effective Raman/fluorescence probe for biolabeling, as well as, for drug delivery. Bio-labeling/drug delivery can be extended to the human blood system, provided one understands the interaction between nanodiamonds and the blood system. Here, the interaction of nanodiamonds (5 and 100 nm) with human red blood cells (RBC) in vitro is discussed. Measurements have been facilitated using Raman spectroscopy, laser scanning fluorescence spectroscopy, and laser diffractometry (ektacytometry). Data on cell viability and hemolytic analysis are also presented. Results indicate that the nanodiamonds in the studied condition do not cause hemolysis, and the cell viability is not affected. Importantly, the oxygenation/deoxygenation process was not found to be altered when nanodiamonds interacted with the RBC. However, the nanodiamond can affect some RBC properties such as deformability and aggregation in a concentration dependent manner. These results suggest that the nanodiamond can be used as an effective bio-labeling and drug delivery tool in ambient conditions, without complicating the blood's physiological conditions. However, controlling the blood properties including deformability of RBCs and rheological properties of blood is necessary during treatment.

Research paper thumbnail of Megakaryocytic differentiation of mouse embryonic stem cells via coculture with immortalized OP9 stromal cells

Experimental cell research, Jan 7, 2015

Established from the calvaria of newborn macrophage colony-stimulating factor (M-CSF)-deficient m... more Established from the calvaria of newborn macrophage colony-stimulating factor (M-CSF)-deficient mice, OP9 is a stromal cell line that used as a feeder layer to support the in vitro differentiation of pluripotent stem cells into various hematopoietic lineage cells, including granulocytes, erythrocytes, lymphocytes, and megakaryocytes. However, as a primary culture cell line, OP9 can be used as stromal cells for only 1 month. Therefore, to obtain functional OP9 cells, numerous M-CSF-deficient newborn mice must be sacrificed. These limitations in some ways restrict the application of OP9 cells in longterm and largescale experiments. In this study, we used human papillomavirus 16 E6 and E7 genes to generate immortalized OP9 stromal cells, designated I-OP9 cells, and then tested their ability to support the megakaryocytic differentiation of pluripotent stem cells in vitro. I-OP9 cells have similar morphology and properties as do parental OP9 cells, and, as expected, have an extended life...

Research paper thumbnail of Endothelial Cell Sensitization by Death Receptor Fractions of an Anti-Dengue Nonstructural Protein 1 Antibody Induced Plasma Leakage, Coagulopathy, and Mortality in Mice

Journal of immunology (Baltimore, Md. : 1950), Jan 15, 2015

The mechanisms leading to the life-threatening dengue hemorrhagic fever (DHF) remain elusive. DHF... more The mechanisms leading to the life-threatening dengue hemorrhagic fever (DHF) remain elusive. DHF preferentially occurs during secondary dengue infections, suggesting that aberrant immune responses are involved in its development. We previously demonstrated that the autoantibodies elicited by dengue virus (DENV) nonstructural protein 1 (NS1; anti-NS1 Igs) induce plasma leakage and mortality in mice with warfarinized anticoagulant suppression. However, the involved pathogenic Ig fractions of anti-NS1 Igs remain unclear. In this study, the autoreactive Igs in patients with DHF and in NS1-immunized rabbits crossreacted with TNF-related apoptosis-inducing ligand receptor 1 (death receptor [DR]4). Challenges with the DENV in a subcytotoxic dose sensitized endothelial cells to apoptosis. Treatments with the autoantibodies induced proapoptotic activities and suppressed the surface expression of endothelial anticoagulant thrombomodulin. Combined treatments comprising the DENV and DR4 affini...

Research paper thumbnail of Antibacterial property of Ag nanoparticle-impregnated N-doped titania films under visible light

Scientific Reports, 2015

Photocatalysts produce free radicals upon receiving light energy; thus, they possess antibacteria... more Photocatalysts produce free radicals upon receiving light energy; thus, they possess antibacterial properties. Silver (Ag) is an antibacterial material that disrupts bacterial physiology. Our previous study reported that the high antibacterial property of silver nanoparticles on the surfaces of visible light-responsive nitrogen-doped TiO 2 photocatalysts [TiO 2 (N)] could be further enhanced by visible light illumination. However, the major limitation of this Ag-TiO 2 composite material is its durability; the antibacterial property decreased markedly after repeated use. To overcome this limitation, we developed TiO 2 (N)/Ag/TiO 2 (N) sandwich films in which the silver is embedded between two TiO 2 (N) layers. Various characteristics, including silver and nitrogen amounts, were examined in the composite materials. Various analyses, including electron microscopy, energy dispersive spectroscopy, X-ray diffraction, and ultraviolet-visible absorption spectrum and methylene blue degradation rate analyses, were performed. The antibacterial properties of the composite materials were investigated. Here we revealed that the antibacterial durability of these thin films is substantially improved in both the dark and visible light, by which bacteria, such as Escherichia coli, Streptococcus pyogenes, Staphylococcus aureus, and Acinetobacter baumannii, could be efficiently eliminated. This study demonstrated a feasible approach to improve the visible-light responsiveness and durability of antibacterial materials that contain silver nanoparticles impregnated in TiO 2 (N) films.

Research paper thumbnail of The Interaction of Protein-Modified Nanodiamond with Bacterial Cells

The nanometer-sized diamond functionalizing and optimization of this process are studied. To crea... more The nanometer-sized diamond functionalizing and optimization of this process are studied. To create the functional groups on the nanodiamond surface the carboxylation/oxidization of 100 nm nanodiamonds was applied and its IR spectra were analyzed. The surface functionalizing was followed by conjugating with protein (lysozyme) via physical adsorption. Nanodiamond-protein interaction was analyzed using FTIR spectroscopy. The interaction of lysozyme-nanodiamond conjugates with E. Coli bacteria was observed by analyzing the adsorbed lysozyme antibacterial activity. Nanodiamond-lysozyme conjugates displayed high activity, equivalent to activity of lysozyme in solution. The results demonstrated that the lysozyme preserved its functionality in conjugates with nanodiamond, while in the same time nanodiamonds can serve as probe using spectroscopic methods.

Research paper thumbnail of Nanodiamonds protect skin from ultraviolet B-induced damage in mice

Journal of nanobiotechnology, 2015

Solar ultraviolet (UV) radiation causes various deleterious effects, and UV blockage is recommend... more Solar ultraviolet (UV) radiation causes various deleterious effects, and UV blockage is recommended for avoiding sunburn. Nanosized titanium dioxide and zinc oxide offer effective protection and enhance cosmetic appearance but entail health concerns regarding their photocatalytic activity, which generates reactive oxygen species. These concerns are absent in nanodiamonds (NDs). Among the UV wavelengths in sunlight, UVB irradiation primarily threatens human health. The efficacy and safety of NDs in UVB protection were evaluated using cell cultures and mouse models. We determined that 2 mg/cm(2) of NDs efficiently reduced over 95% of UVB radiation. Direct UVB exposure caused cell death of cultured keratinocyte, fibroblasts and skin damage in mice. By contrast, ND-shielding significantly protected the aforementioned pathogenic alterations in both cell cultures and mouse models. NDs are feasible and safe materials for preventing UVB-induced skin damage.

Research paper thumbnail of Acquired coagulant factor VIII deficiency induced by Bacillus anthracis lethal toxin in mice

Virulence, Jan 23, 2015

Mice treated with anthrax lethal toxin (LT) exhibit hemorrhage caused by unknown mechanisms. More... more Mice treated with anthrax lethal toxin (LT) exhibit hemorrhage caused by unknown mechanisms. Moreover, LT treatment in mice induced liver damage. In this study, we hypothesized that a suppressed coagulation function may be associated with liver damage, because the liver is the major producing source of coagulation factors. The hepatic expression of coagulant factors and the survival rates were analyzed after cultured cells or mice were exposed to LT. In agreement with our hypothesis, LT induces cytotoxicity against hepatic cells in vitro. In addition, suppressed expression of coagulation factor VIII (FVIII) in the liver is associated with a prolonged plasma clotting time in LT-treated mice, suggesting a suppressive role of LT in coagulation. Accordingly, we further hypothesized that a loss-of-function approach involving treatments of an anticoagulant should exacerbate LT-induced abnormalities, whereas a gain-of-function approach involving injections of recombinant FVIII to complemen...

Research paper thumbnail of Differential regulation of caspase-2 in MPP(+)-induced apoptosis in primary cortical neurons

Experimental cell research, 2015

Parkinson׳s disease (PD), among the most common neurodegenerative diseases worldwide for which th... more Parkinson׳s disease (PD), among the most common neurodegenerative diseases worldwide for which there is no cure, is characterized as progressive dopaminergic neuron loss in the substantia nigra through an unknown mechanism. Administering 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) causes neuronal cell death and Parkinsonism in humans. Commonly used in animal models of PD, MPTP can metabolize to 1-methyl-4-phenylpyridinium (MPP(+)); however, the detailed mechanism through which MPP(+) causes neuronal cell death remains undetermined. Previous reports have indicated those knockout mice with Bcl-2 associated protein X (Bax) or caspase-2, two mitochondrial outer membrane permeabilization inducers, are resistant to MPTP administration, suggesting that mitochondria are involved in MPP(+)-triggered apoptosis. Our previous study showed that MPP(+)-triggered apoptosis can be distinguished from spontaneous apoptosis of primary cortical neurons. In the present study, we verified the ...

Research paper thumbnail of Erythrocytic Mobilization Enhanced by the Granulocyte Colony-Stimulating Factor Is Associated with Reduced Anthrax-Lethal-Toxin-Induced Mortality in Mice

PLoS ONE, 2014

Anthrax lethal toxin (LT), one of the primary virulence factors of Bacillus anthracis, causes ant... more Anthrax lethal toxin (LT), one of the primary virulence factors of Bacillus anthracis, causes anthrax-like symptoms and death in animals. Experiments have indicated that levels of erythrocytopenia and hypoxic stress are associated with disease severity after administering LT. In this study, the granulocyte colony-stimulating factor (G-CSF) was used as a therapeutic agent to ameliorate anthrax-LT-and spore-induced mortality in C57BL/6J mice. We demonstrated that G-CSF promoted the mobilization of mature erythrocytes to peripheral blood, resulting in a significantly faster recovery from erythrocytopenia. In addition, combined treatment using G-CSF and erythropoietin tended to ameliorate B. anthracis-spore-elicited mortality in mice. Although specific treatments against LT-mediated pathogenesis remain elusive, these results may be useful in developing feasible strategies to treat anthrax.

Research paper thumbnail of Erythropoiesis Suppression Is Associated with Anthrax Lethal Toxin-Mediated Pathogenic Progression

PLoS ONE, 2013

Anthrax is a disease caused by the bacterium Bacillus anthracis, which results in high mortality ... more Anthrax is a disease caused by the bacterium Bacillus anthracis, which results in high mortality in animals and humans. Although some of the mechanisms are already known such as asphyxia, extensive knowledge of molecular pathogenesis of this disease is deficient and remains to be further investigated. Lethal toxin (LT) is a major virulence factor of B. anthracis and a specific inhibitor/protease of mitogen-activated protein kinase kinases (MAPKKs). Anthrax LT causes lethality and induces certain anthrax-like symptoms, such as anemia and hypoxia, in experimental mice. Mitogen-activated protein kinases (MAPKs) are the downstream pathways of MAPKKs, and are important for erythropoiesis. This prompted us to hypothesize that anemia and hypoxia may in part be exacerbated by erythropoietic dysfunction. As revealed by colony-forming cell assays in this study, LT challenges significantly reduced mouse erythroid progenitor cells. In addition, in a proteolytic activity-dependent manner, LT suppressed cell survival and differentiation of cord blood CD34 + -derived erythroblasts in vitro. Suppression of cell numbers and the percentage of erythroblasts in the bone marrow were detected in LT-challenged C57BL/6J mice. In contrast, erythropoiesis was provoked through treatments of erythropoietin, significantly ameliorating the anemia and reducing the mortality of LT-treated mice. These data suggested that suppressed erythropoiesis is part of the pathophysiology of LT-mediated intoxication. Because specific treatments to overcome LT-mediated pathogenesis are still lacking, these efforts may help the development of effective treatments against anthrax.

Research paper thumbnail of RECOMBINANT SNAKE DISINTEGRINS USED FOR MAMMALIAN INTEGRIN STUDY

Toxin Reviews, 2005

ABSTRACT

Research paper thumbnail of RHODOSTOMIN, A SNAKE VENOM DISINTEGRIN, SERVED AS A MOLECULAR TOOL TO DISSECT THE INTEGRIN FUNCTION

Toxin Reviews, 2007

ABSTRACT

Research paper thumbnail of Correction: The Use of Nanoscale Visible Light-Responsive Photocatalyst TiO 2 -Pt for the Elimination of Soil-Borne Pathogens

PLoS ONE, 2012

Exposure to the soil-borne pathogens Burkholderia pseudomallei and Burkholderia cenocepacia can l... more Exposure to the soil-borne pathogens Burkholderia pseudomallei and Burkholderia cenocepacia can lead to severe infections and even mortality. These pathogens exhibit a high resistance to antibiotic treatments. In addition, no licensed vaccine is currently available. A nanoscale platinum-containing titania photocatalyst (TiO 2 -Pt) has been shown to have a superior visible light-responsive photocatalytic ability to degrade chemical contaminants like nitrogen oxides. The antibacterial activity of the catalyst and its potential use in soil pathogen control were evaluated. Using the plating method, we found that TiO 2 -Pt exerts superior antibacterial performance against Escherichia coli compared to other commercially available and laboratory prepared ultraviolet/visible light-responsive titania photocatalysts. TiO 2 -Pt-mediated photocatalysis also affectively eliminates the soil-borne bacteria B. pseudomallei and B. cenocepacia. An air pouch infection mouse model further revealed that TiO 2 -Pt-mediated photocatalysis could reduce the pathogenicity of both strains of bacteria. Unexpectedly, water containing up to 10% w/v dissolved soil particles did not reduce the antibacterial potency of TiO 2 -Pt, suggesting that the TiO 2 -Pt photocatalyst is suitable for use in soil-contaminated environments. The TiO 2 -Pt photocatalyst exerted superior antibacterial activity against a broad spectrum of human pathogens, including B. pseudomallei and B. cenocepacia. Soil particles (,10% w/v) did not significantly reduce the antibacterial activity of TiO 2 -Pt in water. These findings suggest that the TiO 2 -Pt photocatalyst may have potential applications in the development of bactericides for soilborne pathogens.

Research paper thumbnail of Visible Light Responsive Photocatalyst Induces Progressive and Apical-Terminus Preferential Damages on Escherichia coli Surfaces

PLoS ONE, 2011

Background: Recent research shows that visible-light responsive photocatalysts have potential usa... more Background: Recent research shows that visible-light responsive photocatalysts have potential usage in antimicrobial applications. However, the dynamic changes in the damage to photocatalyzed bacteria remain unclear.

Research paper thumbnail of Suppressive Effects of Anthrax Lethal Toxin on Megakaryopoiesis

PLoS ONE, 2013

Anthrax lethal toxin (LT) is a major virulence factor of Bacillus anthracis. LT challenge suppres... more Anthrax lethal toxin (LT) is a major virulence factor of Bacillus anthracis. LT challenge suppresses platelet counts and platelet function in mice, however, the mechanism responsible for thrombocytopenia remains unclear. LT inhibits cellular mitogenactivated protein kinases (MAPKs), which are vital pathways responsible for cell survival, differentiation, and maturation. One of the MAPKs, the MEK1/2-extracellular signal-regulated kinase pathway, is particularly important in megakaryopoiesis. This study evaluates the hypothesis that LT may suppress the progenitor cells of platelets, thereby inducing thrombocytopenic responses. Using cord blood-derived CD34 + cells and mouse bone marrow mononuclear cells to perform in vitro differentiation, this work shows that LT suppresses megakaryopoiesis by reducing the survival of megakaryocytes. Thrombopoietin treatments can reduce thrombocytopenia, megakaryocytic suppression, and the quick onset of lethality in LT-challenged mice. These results suggest that megakaryocytic suppression is one of the mechanisms by which LT induces thrombocytopenia. These findings may provide new insights for developing feasible approaches against anthrax.

Research paper thumbnail of The Use of Nanoscale Visible Light-Responsive Photocatalyst TiO2-Pt for the Elimination of Soil-Borne Pathogens

PLoS ONE, 2012

Exposure to the soil-borne pathogens Burkholderia pseudomallei and Burkholderia cenocepacia can l... more Exposure to the soil-borne pathogens Burkholderia pseudomallei and Burkholderia cenocepacia can lead to severe infections and even mortality. These pathogens exhibit a high resistance to antibiotic treatments. In addition, no licensed vaccine is currently available. A nanoscale platinum-containing titania photocatalyst (TiO 2 -Pt) has been shown to have a superior visible light-responsive photocatalytic ability to degrade chemical contaminants like nitrogen oxides. The antibacterial activity of the catalyst and its potential use in soil pathogen control were evaluated. Using the plating method, we found that TiO 2 -Pt exerts superior antibacterial performance against Escherichia coli compared to other commercially available and laboratory prepared ultraviolet/visible light-responsive titania photocatalysts. TiO 2 -Pt-mediated photocatalysis also affectively eliminates the soil-borne bacteria B. pseudomallei and B. cenocepacia. An air pouch infection mouse model further revealed that TiO 2 -Pt-mediated photocatalysis could reduce the pathogenicity of both strains of bacteria. Unexpectedly, water containing up to 10% w/v dissolved soil particles did not reduce the antibacterial potency of TiO 2 -Pt, suggesting that the TiO 2 -Pt photocatalyst is suitable for use in soil-contaminated environments. The TiO 2 -Pt photocatalyst exerted superior antibacterial activity against a broad spectrum of human pathogens, including B. pseudomallei and B. cenocepacia. Soil particles (,10% w/v) did not significantly reduce the antibacterial activity of TiO 2 -Pt in water. These findings suggest that the TiO 2 -Pt photocatalyst may have potential applications in the development of bactericides for soilborne pathogens.

Research paper thumbnail of Cell adhesion as a novel approach to determining the cellular binding motif on the severe acute respiratory syndrome coronavirus spike protein

Journal of Virological Methods, 2014

Please cite this article in press as: Chang, H.-H., et al., Cell adhesion as a novel approach to ... more Please cite this article in press as: Chang, H.-H., et al., Cell adhesion as a novel approach to determining the cellular binding motif on the severe acute respiratory syndrome coronavirus spike protein. J. Virol. Methods (2014), http://dx.

Research paper thumbnail of Antiplatelet Activities of Anthrax Lethal Toxin Are Associated with Suppressed p42/44 and p38 Mitogen‐Activated Protein Kinase Pathways in the Platelets

The Journal of Infectious Diseases, 2005

Anthrax lethal toxin (LT) is the major virulence factor produced by Bacillus anthracis, but the m... more Anthrax lethal toxin (LT) is the major virulence factor produced by Bacillus anthracis, but the mechanism by which it induces high mortality remains unclear. We found that LT treatment could induce severe hemorrhage in mice and significantly suppress human whole-blood clotting and platelet aggregation in vitro. In addition, LT could inhibit agonist-induced platelet surface P-selectin expression, resulting in the inhibition of platelet-endothelial cell engagements. Data from Western blot analysis indicated that LT treatment resulted in the suppression of p42/44 and p38 mitogen-activated protein kinase pathways in platelets. Combined treatments with LT and antiplatelet agents such as aspirin and the RGD-containing disintegrin rhodostomin significantly increased mortality in mice. Our data suggest that platelets are a pathogenic target for anthrax LT.

Research paper thumbnail of Facilitation of Cell Adhesion by Immobilized Dengue Viral Nonstructural Protein 1 (NS1): Arginine‐Glycine‐Aspartic Acid Structural Mimicry within the Dengue Viral NS1 Antigen

The Journal of Infectious Diseases, 2002

Dengue virus infection causes life-threatening hemorrhagic fever. Increasing evidence implies tha... more Dengue virus infection causes life-threatening hemorrhagic fever. Increasing evidence implies that dengue viral nonstructural protein 1 (NS1) exhibits a tendency to elicit potentially hazardous autoantibodies, which show a wide spectrum of specificity against extracellular matrix and platelet antigens. How NS1 elicits autoantibodies remains unclear. To address the hypothesis that NS1 and matrix proteins may have structural and functional similarity, cell-matrix and cell-NS1 interactions were evaluated using a cell-adhesion assay. The present study showed that dengue NS1 immobilized on coverslips resulted in more cell adhesion than did the control proteins. This cell adhesion was inhibited by peptides containing arginine-glycine-aspartic acid (RGD), a motif important for integrin-mediated cell adhesion. In addition, anti-NS1 antibodies blocked RGD-mediated cell adhesion. Although there is no RGD motif in the NS1 protein sequence, these data indicate that RGD structural mimicry exists within the NS1 antigen.

Research paper thumbnail of Activated protein C ameliorates Bacillus anthracis lethal toxin-induced lethal pathogenesis in rats

Journal of Biomedical Science, 2012

Background: Lethal toxin (LT) is a major virulence factor of Bacillus anthracis. Sprague Dawley r... more Background: Lethal toxin (LT) is a major virulence factor of Bacillus anthracis. Sprague Dawley rats manifest pronounced lung edema and shock after LT treatments, resulting in high mortality. The heart failure that is induced by LT has been suggested to be a principal mechanism of lung edema and mortality in rodents. Since LT-induced death occurs more rapidly in rats than in mice, suggesting that other mechanisms in addition to the heart dysfunction may be contributed to the fast progression of LT-induced pathogenesis in rats. Coagulopathy may contribute to circulatory failure and lung injury. However, the effect of LT on coagulation-induced lung dysfunction is unclear. Methods: To investigate the involvement of coagulopathy in LT-mediated pathogenesis, the mortality, lung histology and coagulant levels of LT-treated rats were examined. The effects of activated protein C (aPC) on LT-mediated pathogenesis were also evaluated.

Research paper thumbnail of The influence of nanodiamond on the oxygenation states and micro rheological properties of human red blood cells <italic>in vitro</italic>

Journal of Biomedical Optics, 2012

Nanodiamond has been proven to be biocompatible and proposed for various biomedical applications.... more Nanodiamond has been proven to be biocompatible and proposed for various biomedical applications. Recently, nanometer-sized diamonds have been demonstrated as an effective Raman/fluorescence probe for biolabeling, as well as, for drug delivery. Bio-labeling/drug delivery can be extended to the human blood system, provided one understands the interaction between nanodiamonds and the blood system. Here, the interaction of nanodiamonds (5 and 100 nm) with human red blood cells (RBC) in vitro is discussed. Measurements have been facilitated using Raman spectroscopy, laser scanning fluorescence spectroscopy, and laser diffractometry (ektacytometry). Data on cell viability and hemolytic analysis are also presented. Results indicate that the nanodiamonds in the studied condition do not cause hemolysis, and the cell viability is not affected. Importantly, the oxygenation/deoxygenation process was not found to be altered when nanodiamonds interacted with the RBC. However, the nanodiamond can affect some RBC properties such as deformability and aggregation in a concentration dependent manner. These results suggest that the nanodiamond can be used as an effective bio-labeling and drug delivery tool in ambient conditions, without complicating the blood's physiological conditions. However, controlling the blood properties including deformability of RBCs and rheological properties of blood is necessary during treatment.