Nontoxic, Biodegradable Hyperbranched Poly(β-amino ester)s for Efficient siRNA Delivery and Gene Silencing.

RNA interference (RNAi)-mediated gene silencing is a promising therapeutic approach to treat various diseases, but safe and efficient delivery remains a major challenge to its clinical application. Non-viral gene vectors, such as poly(β-amino esters) (pBAEs), have emerged as a potential candidate due to their biodegradability, low toxicity profile, ease of synthesis, and high gene transfection efficiency for both DNA and siRNA delivery. However, achieving significant gene silencing using pBAEs often requires a large amount of polymer carrier (with polymer/siRNA weight ratio >100) or high siRNA dose (>100 nM), which might potentially exacerbate toxicity concerns during delivery.

Exploration of photochemical reactions of N-trimethylsilylmethyl-substituted uracil, pyridone, and pyrrolidone derivatives.

Photochemical reactions of N-trimethylsilylmethyl-substituted uracil, pyridone and pyrrolidone derivatives were carried out to determine if silicone containing substituents have an impact on excited state reaction profiles. The results show that ultraviolet irradiation of N-trimethylsilylmethyl substituted uracils in the presence of substituted alkenes leads to efficient formation of both dimeric and cross [2+2]-cycloaddition products. Qualitatively similar observations were made in a study of the photochemistry of N-trimethylsilylmethyl-2-pyridone.

Fabrication of a microarray using a combination of the large circular sense and antisense DNA.

In the present study, single-stranded large circular (LC)-sense molecules were utilized as probes for DNA microarrays and showed stronger binding signals than those of PCR-amplified cDNA probes. A microarray experiment using 284 LC-sense DNA probes found 6 upregulated and 7 downregulated genes in A549 cells as compared to WI38VA13 cells. Repeated experiments showed largely consistent results, and microarray data strongly correlated with data acquired from quantitative real-time RT-PCR.

Water sorption and dynamic mechanical properties of dentin adhesives with a urethane-based multifunctional methacrylate monomer.

Objectives: Our previous study showed the synthesis and characterization of a novel urethane-linked trimethacrylate monomer for use as a co-monomer in dentin adhesives. The objective of this work was to further investigate the performance of dentin adhesives containing a new monomer, with particular emphasis on the water sorption and viscoelastic behavior of the crosslinked networks.

Materials And Methods: Dentin adhesives contained 2,2-bis[4-(2-hydroxy-3-methacryloxypropoxy) phenyl]-propane (BisGMA), 2-hydroxyethyl methacrylate (HEMA), and a new multifunctional methacrylate with urethane-linked groups-1,1,1-tri-[4-(methacryloxyethylaminocarbonyloxy)-phenyl]ethane (MPE) and were photo-polymerized in the presence or absence of water.

Enzyme-catalyzed hydrolysis of dentin adhesives containing a new urethane-based trimethacrylate monomer.

A new trimethacrylate monomer with urethane-linked groups, 1,1,1-tri-[4-(methacryloxyethylamino-carbonyloxy)-phenyl]ethane (MPE), was synthesized, characterized, and used as a comonomer in dentin adhesives. Dentin adhesives containing 2-hydroxyethyl methacrylate (HEMA, 45% w/w) and 2,2-bis[4(2-hydroxy-3-methacryloyloxy-propyloxy)-phenyl] propane (BisGMA, 30% w/w) in addition to MPE (25% w/w) were formulated with H(2)O at 0 (MPE0), 8 (MPE8), and 16 wt % water (MPE16) to simulate the wet demineralized dentin matrix and compared with controls [HEMA /BisGMA, 45/55 w/w, at 0 (C0), 8 (C8), and 16 wt % water (C16)]. The new adhesive showed a degree of double bond conversion and mechanical properties comparable with control, with good penetration into the dentin surface and a uniform adhesive/dentin interface.

Synthesis of novel cholesterol-based cationic lipids for gene delivery.

The new cholesterol-based cationic lipids B, C, and D with an ether linked spacer were synthesized by using aminopropyl chain extension with acrylonitrile. The cholesterol-based cationic lipid A with carbamoyl linkage were also synthesized in order to compare the difference in transfection efficiency of the two linkage types. To this end, GFP expression of these cationic lipids was confirmed respectively.

Dynamic mechanical analysis and esterase degradation of dentin adhesives containing a branched methacrylate.

A study of the dynamic mechanical properties and the enzymatic degradation of new dentin adhesives containing a multifunctional methacrylate are described. Adhesives contained 2-hydroxyethyl methacrylate, 2,2-bis[4-(2-hydroxy-3-methacryloxypropoxy) phenyl]-propane, and a new multifunctional methacrylate with a branched side chain-trimethylolpropane mono allyl ether dimethacrylate (TMPEDMA). Adhesives were photopolymerized in the presence of 0, 8, and 16 wt % water to simulate wet bonding conditions in the mouth and compared with control adhesives.

Sanguinarine induces apoptosis in A549 human lung cancer cells primarily via cellular glutathione depletion.

Sanguinarine is a plant-derived benzophenanthridine alkaloid and has been shown to possess anti-tumor activities against various cancer cells. In this study, we investigated whether sanguinarine induces apoptosis in A549 human lung cancer cells. Treatment of A549 cells with sanguinarine induced apoptosis in a dose- and time-dependent manner.

Bioactive glass-ionomer cement with potential therapeutic function to dentin capping mineralization.

We have developed a novel bioactive resin-modified glass-ionomer cement system with therapeutic function to dentin capping mineralization. In the system, the newly synthesized star-shape poly(acrylic acid) was formulated with water, Fuji II LC filler, and bioactive glass S53P4 to form resin-modified glass-ionomer cement. Compressive strength (CS) was used as a screening tool for evaluation.

Cadmium specifically induces MKP-1 expression via the glutathione depletion-mediated p38 MAPK activation in C6 glioma cells.

Cadmium is a toxic heavy metal and an environmental pollutant. Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) is a negative regulator of the family of MAPK. In this study, we investigated the effect of heavy metals on MKP-1 expression in C6 rat glioma cells.

Enzymatic biodegradation of HEMA/bisGMA adhesives formulated with different water content.

Dentin adhesives may undergo phase separation when bonding to wet demineralized dentin. We hypothesized that adhesives exhibiting phase separation will experience enhanced biodegradation of methacrylate ester groups. The objective of this project was to study the effect of enzyme-exposure on the release of methacrylic acid (MAA) and 2-hydroxyethyl methacrylate (HEMA) from adhesives formulated under conditions simulating wet bonding.

Preparation and Properties of Novel Dentin Adhesives with Esterase Resistance.

A new methacrylate monomer, trimethylolpropane mono allyl ether dimethacrylate (TMPEDMA), was synthesized and evaluated. This branched methacrylate was designed to increase esterase-resistance when incorporated into conventional HEMA (2-hydroxyethyl methacrylate)/BisGMA (2,2-bis[4(2-hydroxy-3-methacryloyloxy-propyloxy)-phenyl] propane) dental adhesives. The new adhesives, HEMA/BisGMA/TMPEDMA in a 45/30/25 (w/w) ratio were formulated with H(2)O at 0 (A0T) and 8 wt % water (A8T) and compared with control adhesives (HEMA/BisGMA, 45/55 (w/w), at 0 (A0) and 8 wt % (A8) water).

Prevention of CCl4-induced liver cirrhosis by ribbon antisense to transforming growth factor-beta1.

Transforming growth factor-beta1 (TGF-beta1) is an important mediator of tissue fibrosis, including liver cirrhosis. Ribbon-type antisense oligonucleotide to TGF-beta1 (TGF-beta1 RiAS) was designed and combined with cationic peptide derived from the nuclear localization signal of human immunodeficiency virus-1 Tat protein for enhanced cellular uptake. When Hepa1c1c7 cells were transfected with TGF-beta1 RiAS, the level of TGF-beta1 mRNA was reduced by >70%.

Marked transfection enhancement by the DPL (DNA/peptide/lipid) complex.

A short peptide, corresponding to the nuclear localization signal of the human immunodeficiency virus-1 Tat protein, Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg, was modified by adding a cysteine residue at the COOH terminus. The peptide was mixed with a reporter plasmid, and then with cationic lipids, to form a tripartite complex, DNA/peptide/lipid (DPL). Various cell lines were treated with the DPL complex and compared for transfection efficiency with those of the conventional DNA/lipid (DL) complex.

Dexamethasone suppresses interleukin-1beta-induced human beta-defensin 2 mRNA expression: involvement of p38 MAPK, JNK, MKP-1, and NF-kappaB transcriptional factor in A549 cells.

Human beta-defensin (HBD)-2 is an inducible antimicrobial peptide that plays an important role in innate immunity. Glucocorticoids, on the other hand, exert immunosuppressive and anti-inflammatory actions. We have previously reported that interleukin (IL)-1beta induces HBD-2 mRNA expression through the activation of nuclear factor-kappaB (NF-kappaB) transcriptional factor, as well as p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), or phosphatidylinositol-3-kinase/AKT in A549 cells.

Glucosamine hydrochloride specifically inhibits COX-2 by preventing COX-2 N-glycosylation and by increasing COX-2 protein turnover in a proteasome-dependent manner.

COX-2 and its products, including prostaglandin E(2), are involved in many inflammatory processes. Glucosamine (GS) is an amino monosaccharide and has been widely used for alternative regimen of (osteo) arthritis. However, the mechanism of action of GS on COX-2 expression remains unclear.

A novel light-cured glass-ionomer system for improved dental restoratives.

A novel light-cured glass-ionomer cement (LCGIC) system based on the 4-arm star-shape poly(acrylic acid) (AA) tethered with glycidyl methacrylate has been developed. The 4-arm poly(AA) polymer was synthesized using atom-transfer radical polymerization. The purified polymer was used to formulate with water and Fuji II LC filler to form LCGICs.

Triptolide suppresses interleukin-1beta-induced human beta-defensin-2 mRNA expression through inhibition of transcriptional activation of NF-kappaB in A549 cells.

The immunosuppressive effect of triptolide has been associated with suppression of T-cell activation. However, the immunosuppressive effects of triptolide on innate immunity in the epithelial barrier remain to be elucidated. Human beta-defensin (HBD)-2 is an inducible antimicrobial peptide and plays an important role in the innate immunity.

Leptomycin B, a metabolite of Streptomyces, inhibits the expression of inducible nitric oxide synthase in BV2 microglial cells.

Overexpression of inducible nitric oxide synthase (iNOS) and the resultant overproduction of NO has been implicated in neuronal inflammatory diseases. Leptomycin B (LMB), a metabolite of Streptomyces, has been identified as a specific inhibitor of CRM1 nuclear export receptor. In this study, we evaluated the effect of LMB on lipopolysaccharide (LPS)-induced iNOS expression in BV2 cells, a murine microglial cells and the associated mechanisms.

A novel comonomer-free light-cured glass-ionomer cement for reduced cytotoxicity and enhanced mechanical strength.

Objective: The objective of this study was to develop a novel comonomer-free light-cured glass-ionomer system based on the 4-arm star-shape poly(acrylic acid). The mechanical strengths and in vitro cytotoxicity of the formed system were evaluated and compared with those of several representative commercial glass-ionomer cements.

Materials And Methods: The 4-arm poly(acrylic acid) was synthesized using ATRP and tethered with glycidyl methacrylate (GM).

Novel injectable and in situ curable glycolide/lactide based biodegradable polymer resins and composites.

Novel in situ polymerizable liquid three-arm biodegradable oligomeric polyesters based upon glycolic acid (GA), L-lactic acid (LLA), and their copolymers are synthesized and characterized. Injectable and in situ curable polymer neat resins and their composites formulated with bioabsorbable beta-tricalcium phosphate are prepared at room temperature using photo- and redox-initiation systems, respectively. The cured neat resins show the initial compressive yield strength (YCS, MPa), modulus (M, MPa), ultimate compressive strength (UCS, MPa), and toughness (T, kN mm), ranging from 4.

Preparation, formulation and evaluation of novel photo-cured glass ionomers based on co-polymers of (meth)acrylated amino acids.

A novel photo-cured amino-acid-constructed glass-ionomer cement system has been developed. Glutamic acid- and beta-alanine-based methacrylate and acrylate derivatives were synthesized, characterized and used to construct the polyalkenoic acids and formulated with water and Fuji II glass filler to form self-cured cement. Compressive strength (CS) of the cement and viscosity of the liquid were used as tools for evaluation.

Synthesis and preparation of novel 4-arm star-shape poly(carboxylic acid)s for improved light-cured glass-ionomer cements.

Objective: The objective of this study was to synthesize and characterize novel 4-arm star-shape poly(acrylic acid)s (poly(AA)s) via atom-transfer radical polymerization (ATRP) technique, tether in situ light-curable methacrylate functionalities onto the poly(AA) backbone, use these star-shape poly(AA)s to formulate the light-cured glass-ionomer cements (LCGICs), and evaluate the mechanical strengths of the formed cements.

Materials And Methods: The 4-arm poly(AA)s were synthesized using ATRP and tethered with either 2-isocyanatoethyl methacrylate (IEM) or glycidyl methacrylate (GM). The polymers were formulated with 2-hydroxyethyl methacrylte (HEMA) or methacryloyl beta-alanine (MBA), water, initiators, and Fuji II LC filler.

Novel amino acid-constructed polyalkenoates for dental glass-ionomer restoratives.

Several methacrylate or acrylate derivatives of natural amino acids were synthesized and characterized. Based upon these derivatives, novel amino acid-constructed polyalkenoic acids were prepared and used to formulate glass-ionomer cements (GICs) with Fuji II glass filler. The effects of type of derivatives, molar ratio, molecular weight, and powder/liquid ratio were investigated.

Inhibitory modulation of ATP-sensitive potassium channels by gallate-ester moiety of (-)-epigallocatechin-3-gallate.

(-)-Epigallocatechin-3-gallate (EGCG), a major polyphenolic substance found in green tea, is well recognized to be beneficial for human health. However, it is still controversial as to what dose of this compound is indeed good for human health. Though some recent studies have interestingly reported various beneficial effects of EGCG in cell culture system, however, plasma levels of EGCG attainable by oral regular intake in humans are normally in nanomolar range.