Biomedical subjects

Jia-Cong Shen

Publications and source records attributed to Jia-Cong Shen.

10 recordsLinked to original sources

PubMed2006

Cyclodextrin-derived mimic of glutathione peroxidase exhibiting enzymatic specificity and high catalytic efficiency.

To elucidate the relationships between molecular recognition and catalytic ability, we chose three assay systems using three different thiol substrates, glutathione (GSH), 3-carboxyl-4-nitrobenzenethiol (CNBSH), and 4-nitrobenzenethiol (NBSH), to investigate the glutathione peroxidase (GPx) activities of 2,2'-ditellurobis(2-deoxy-beta-cyclodextrin) (2-TeCD) in the presence of a variety of structurally distinct hydroperoxides (ROOH), H2O2, tert-butyl peroxide (tBuOOH), and cumene peroxide (CuOOH), as the oxidative reagent. A comparative study of the three assay systems revealed that the cyclodextrin moiety of the GPx mimic 2-TeCD endows the molecule with selectivity for ROOH and thiol substrates, and hydrophobic interactions are the most important driving forces in 2-TeCD complexation. Furthermore, in the novel NBSH assay system, 2-TeCD can catalyze the reduction of ROOH about 3.4 x 10(5) times more efficiently than diphenyl diselenide (PhSeSePh), and its second-order rate constants for thiol are similar to some of those of native GPx. This comparative study confirms that efficient binding of the substrate is essential for the catalytic ability of the GPx mimic, and that NBSH is the preferred thiol substrate of 2-TeCD among the chosen thiol substrates. Importantly, the proposed mode of action of 2-TeCD imitates the role played by several possible noncovalent interactions between enzymes and substrates in influencing catalysis and binding.

Catalysis↗

PubMed2006

[Nanobiomaterials].

Nanobiomaterial is a multidisciplinary scientific field with roots in life science, material science and nanotechnology. The basic and application researches of nanobiomaterials have been the hot topic in the materials research for biomedicine and biotechnology, which have developed quickly in biomedical implant and intervention medicine, tissue engineering and regenerative medicine, and drug/gene delivery system. This review focuses on the potential of nanobiomaterials including biocompatible surface, tissue engineering and regenerative materials, new drug/gene delivery system and bioanalysis system, with an attempt to explore their possible applications in clinical practice.

Biocompatible Materials↗

PubMed2005

Novel biomimetic polymersomes as polymer therapeutics for drug delivery.

Novel amphiphilic diblock copolymers, cholesterol-end-capped poly(2-methacryloyloxyethyl phosphorylcholine) (CMPC), which have poly(2-methacryloyloxyethyl phosphorylcholine) (poly(MPC)) as hydrophilic segment and cholesterol as hydrophobic segment, was specially designed as drug delivery systems. Fluorescence probe technique and transmission electron microscope (TEM) characterizations indicated that this novel amphiphilic copolymer formed micelles structure in water and the critical micelle concentration (CMC) was determined to be 1.57 x 10(-7) mol/l. A commercial obtained polymeric amphiphiles, Cholesterol end capped PEO (CPEO), which had a similar structure with CMPC, was used as a control in the cytotoxicity test. While CPEO showed obvious cytotoxicity, cytotoxicity of this novel amphiphiles was not observed as indicated by cell culture. Anti-cancer drug adriamycin (ADR) was incorporated into the micelles by oil-in-water method. The size of the drug-containing micelles was less than 200 nm, and the size distribution of the drug-containing micelles showed a narrow and monodisperse unimodal pattern. The release rate of ADR from the nanosphere was slow and the release continued over 7 days and the release rate decreased with the increase of molecular weights of the copolymer and the amount of the drug entrapped. These experimental results suggested that the nanoparticles prepared from CMPC block copolymers could be a good candidate for injectable drug delivery carrier.

3T3 Cells↗

PubMed2005

Novel biomimetic surfactant: synthesis and micellar characteristics.

Novel biomimetic surfactants based on cholesterol as the hydrophobic segment and poly[2-(methacryloyloxy)ethyl phosphorylcholine] (pMPC) as the hydrophilic segment were synthesized in the present study by atom transfer radical polymerization (ATRP) of 2-(methacryloyloxy)ethyl phosphorylcholine (MPC) using a cholesterol-based macroinitiator. The association behavior of cholesterol-block-poly[2-(methacryloyloxy)ethyl phosphorylcholine] (Chol-pMPCs) in aqueous solution was studied by (1)H NMR spectroscopy, fluorescence probe technique, and atomic force microscopy (AFM). The (1)H NMR spectrum of the polymer in CD(3)OD showed both the cholesterol group and the phosphorylcholine group while the cholesterol group did not appeared in the (1)H NMR spectrum of the polymer in D(2)O, which implied the formation of a micelle structure. Fluorescence excitation spectra of a pyrene probe solubilized in the aggregates of Chol-pMPCs suggested the presence of a critical micelle concentration (cmc) in water. The critical micelle concentrations of the polymers CMPC10, CMPC20 and CMPC40 were determined to be 7.27 x 10(-3), 13.47 x 10(-3), and 20.77 x 10(-3) mg . mL(-1), respectively. AFM images of the aggregates on mica suggested that the pMPC block formed the biocompatible micelle coronas and the cholesterol block formed the hydrophobic micelle cores. These new biomimetic diblock copolymers were evaluated as "stealthy" nanocapsules for the delivery of hydrophobic drugs. The anti-cancer drug adriamycin (ADR) was chosen as a hydrophobic drug to be incorporated into the inner core of the micelles and the morphology of the drug-loaded micelles were observed by AFM.

Biomimetic Materials↗

PubMed2005

Engineering glutathione transferase to a novel glutathione peroxidase mimic with high catalytic efficiency. Incorporation of selenocysteine into a glutathione-binding scaffold using an auxotrophic expression system.

Glutathione peroxidase (GPx, EC 1.11.1.9) protects cells against oxidative damage by catalyzing the reduction of hydroperoxides with glutathione (GSH). Several attempts have been made to imitate its function for mechanical study and for its pharmacological development as an antioxidant. By replacing the active site serine 9 with a cysteine and then substituting it with selenocysteine in a cysteine auxotrophic system, catalytically essential residue selenocysteine was bioincorporated into GSH-specific binding scaffold, and thus, glutathione S-transferase (GST, EC 2.5.1.18) from Lucilia cuprina was converted into a selenium-containing enzyme, seleno-LuGST1-1, by genetic engineering. Taking advantage of the important structure similarities between seleno-LuGST1-1 and naturally occurring GPx in the specific GSH binding sites and the geometric conformation for the active selenocysteine in their common GSH binding domain-adopted thioredoxin fold, the as-generated selenoenzyme displayed a significantly high efficiency for catalyzing the reduction of hydrogen peroxide by glutathione, being comparable with those of natural GPxs. The catalytic behaviors of this engineered selenoenzyme were found to be similar to those of naturally occurring GPx. It exhibited pH and temperature-dependent catalytic activity and a typical ping-pong kinetic mechanism. Engineering GST into an efficient GPx-like biocatalyst provided new proof for the previous assumption that both GPx and GST were evolved from a common thioredoxin-like ancestor to accommodate different functions throughout evolution.

Catalysis↗

PubMed2005

Fabrication of thromboresistant multilayer thin film on plasma treated poly (vinyl chloride) surface.

Layer-by-layer deposited anticoagulant multilayer films were prepared on ammonia plasma treated poly (vinyl chloride) (PVC). Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR) and contact angle results revealed the presence of -NH2 on the ammonia plasma treated PVC surfaces and the layer-by-layer self-assembly process. The stability of multilayer film was studied with the radio labeled method. The remainder bovine serum albumin (BSA) in cross-linked 5(heparin/BSA) multilayer films dipped in phosphate buffered saline (PBS, pH 7.4) was more than 90% in 40 days. The static platelet adhesion result indicated the anticoagulant multilayer films deposited on the plasma treated PVC reduced platelet adhesion drastically and no thrombus forming. The plasma recalcification time revealed that the multilayer modified surfaces greatly prolonged the plasma recalcification time. Such an easy processing and shape-independent method may have good potential for surface modification of cardiovascular devices.

Blood Platelets↗

PubMed2005

The effect of formation of the liquid crystalline phase on the blood compatibility of a cholesterol modified silicone.

Cholesterol modified silicones were synthesized by grafting copolymerization of 10-Cholesteryloxydecanol onto polymethylhydrosiloxane (PMHS). Fourier transform infrared (FT-IR) spectroscopy, proton nuclear magnetic resonance ((1)H-NMR) spectroscopy and gel permeation chromatography (GPC) confirmed the chemical structures of polymers. Differential scanning calorimetry (DSC) and polarized optical microscopy (POM) results indicated the mesogenic properties of those polymers. The modified silicone with 45% 10-Cholesteryloxydecanyl (SC45) indicated obvious thermotropic liquid crystalline transform at about 122-124.9 degrees C. The thermotropic liquid crystalline phase could be retained at room temperature via a special annealing/quenching process. The anneal-quenched film (SC45C) formed continuous liquid crystalline phase, whereas the unannealed films presented amorphous structure. The blood compatibility of the coatings was assessed from SEM observation of the platelet's adhesion to coating surface and plasma recalcification time (PRT). The results revealed that the formation of the liquid crystalline phase could greatly improve the in vitro blood compatibility of the materials. The positive results of liquid crystalline onto haemocompatibility allow broad potential in biomaterials.

Biocompatible Materials↗

PubMed2004

Water-dispersed bone morphogenetic protein nanospheres prepared by co-precipitation method.

A modified complex coacervation-co-precipitation method was used to prepare bone morphogenetic protein (BMP)-loaded nanospheres. Three natural polymers were used as packing materials to obtain nanoscale delivery device for BMP, in the presence of phosphatidylcholine functioning as stabilizer. Positively charged polysaccharide, N,N-diethylaminoethyl dextran (DEAE-dextran) tended to form stable, uniform and smaller size particles carrying BMP. Negatively charged bovine serum albumin (BSA) induced precipitation of the produced BMP particles due to its weak interaction with BMP molecules, although it produced nanosized BMP spheres. While collagen, a weakly positively charged protein shaped larger particles due to the strong interaction among themselves. A mechanism of co-precipitation process was also deduced to depict the formation of stable nanospheres.

Animals↗

PubMed2004

A novel crosslinkable polymer as drug-loaded coating for biomedical device.

A novel copolymer has been synthesized by the radical polymerization of poly (ethylene oxide) methacrylate, stearyl methacrylate, hydroxypropyl methacrylate and trimethoxysilylpropyl methacrylate. The polymer was characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance (1H-NMR) spectroscopy and gel permeation chromatography. The crosslinkable coating was prepared by dip-coating 5mg/ml solution in tetrahydrofuran onto glass substrate. A stable crosslinked coating was obtained after curing the coating at 70 degrees C for 9 h. Contact angle results indicated the possible reorganization of the surface amphiphilic molecule which interpreted the excellent biocompatibility revealed by the results of the platelet adhesion and plasma recalcification time. Rhodamine S and Cibacron Blue were used as model drugs to prepare drug-containing coating at the same conditions. Drug-releasing curves indicated that the mechanism of the release is approximately Fickian release.

Blood Coagulation↗

PubMed2001

Expression of HIV-2 gp 105 Gene and Characterization of gp105 in Methyltrophic Pichia pastoris.

To explore a new approach to express HIV-2 external glycoprotein gp105 in methyltrophic yeast, Pichia pastoris, the gp 105 gene was obtained by PCR amplification and was cloned into the secreted expression vector pHILS1. The positive recombinant Pichia pastoris strains were screened and identified by PCR after electroporation and induction by methanol of the gp105 expression. SDS-PAGE and Western blot analyses showed that gp105, unlike gp120 from HIV-1, could be secreted into medium by recombinant Pichia pastoris strain, and the expressed product of a 90 kD glycoprotein showed satisfactory antigenicity with specific antibody.

Journal Article↗