Self-crosslinked and reducible fusogenic peptides for intracellular delivery of siRNA.

A novel self-crosslinked and reducible peptide was synthesized for stable formation of nanoscale complexes with an siRNA-PEG conjugate to enhance transfection efficiency in serum containing condition without compromising cytotoxicity. A fusogenic peptide, KALA, with two cysteine residues at both terminal ends was crosslinked via disulfide linkages under mild DMSO oxidation condition. The reducible crosslinked KALA (cl-KALA) was used to form nano-complexes with green fluorescent protein (GFP) siRNA.

Water-free microencapsulation of proteins within PLGA microparticles by spray drying using PEG-assisted protein solubilization technique in organic solvent.

Poly(d,l-lactic-co-glycolic acid) (PLGA) microparticles encapsulating therapeutic proteins were prepared under a water-free formulation condition. Bovine serum albumin (BSA) and recombinant human growth hormone (rhGH) were homogeneously solubilized as nano-scale complexes in methylene chloride phase by using polyethylene glycol (PEG) as a complex-forming agent. The organic phase containing dissolved PLGA and PEG/protein complexes was directly spray dried to obtain PLGA microparticles encapsulating proteins.

Synthesis, characterization, and intracellular delivery of reducible heparin nanogels for apoptotic cell death.

Reducible heparin nanogels cross-linked with disulfide linkages were developed for efficient cellular uptake of therapeutic heparin to induce apoptotic cell death. The heparin nanogels were synthesized by forming nanocomplexes between thiolated heparin and poly(ethylene glycol) in a selected organic solvent, and subsequently producing intermolecular disulfide bonds between thiolated heparin molecules by ultrasonication. The resultant heparin nanogels had a stable structure with an average diameter of 248.

Climatic influence on the prevalence of noncutaneous disease flare in systemic lupus erythematosus in Hong Kong.

Objective: It is generally agreed that there is a seasonal variation in the prevalence of cutaneous manifestations of systemic lupus erythematosus (SLE). We investigated whether there is seasonal variation in the incidence of noncutaneous lupus flare in Hong Kong.

Methods: We reviewed all noncutaneous lupus flare in 222 consecutive patients with SLE followed in our clinic from 1995 to 2005.

Enhanced intracellular delivery of quantum dot and adenovirus nanoparticles triggered by acidic pH via surface charge reversal.

Quantum dot (QD) and adenovirus (ADV) nanoparticles were surface-modified with graft copolymers that exhibited a charge reversal behavior under acidic condition. Poly(L-lysine) (PLL) was grafted with multiple biotin-PEG chains (biotin-PEG-PLL graft copolymer), and the remaining primary amine groups in the PLL backbone were postmodified using citraconic anhydride, a pH-sensitive primary amine blocker, to generate carboxylate groups. The surfaces of streptavidin-conjugated QDs were modified with citraconylated biotin-PEG-PLL copolymer, producing net negatively charged QD nanoparticles.

Dissolution of biomacromolecules in organic solvents by nano-complexing with poly(ethylene glycol).

Various biomacromolecules (BMs) such as proteins, DNA, and carbohydrates are extremely difficult to be dissolved in a single organic solvent phase for sustained release or targeted delivery formulation. In this study, three different BMs could be solubilized in selected organic solvents by forming poly(ethylene glycol) (PEG)-assisted nano-complexes while maintaining their structural integrity. Dynamic light scattering (DLS) and atomic force microscopy (AFM) analysis revealed that proteins, DNA, and carbohydrate polymers could be nano-complexed with PEG in various organic solvents.

Synthesis, characterization, antitumor activity of pluronic mimicking copolymer micelles conjugated with doxorubicin via acid-cleavable linkage.

Pluronic mimicking poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymer having multiple hydroxyl groups in the PPO middle segment (core-functionalized Pluronic: CF-PLU) was synthesized for conjugation of doxorubicin (DOX). DOX was conjugated on the multiple hydroxyl groups of CF-PLU via an acid-labile hydrazone linkage (CF-PLU-DOX). In aqueous solution, CF-PLU-DOX copolymers self-assembled to form a core/shell-type micelle structure consisting of a hydrophobic DOX-conjugated PPO core and a hydrophilic PEO shell layer.

Paroxetine versus placebo and other agents for depressive disorders: a systematic review and meta-analysis.

Objective: To compare paroxetine with placebo and other antidepressants across multiple efficacy and tolerability outcomes.

Data Sources: Searches were conducted in MEDLINE (1966-2004), EMBASE (1980-2004), CINAHL (1982-2004), all Evidence-Based Medicine Reviews (1991-2004), HealthSTAR (1975-2004), BIOSIS (1980-2004), and PsycINFO (1840-2004). Medical Subject Headings (MeSH) included "paroxetine" OR "Paxil" exploded.

Epidermal growth factor (EGF) receptor targeted delivery of PEGylated adenovirus.

A biotin-polyethylene glycol (PEG)-epidermal growth factor (EGF) conjugate was immobilized onto the surface of avidin-modified adenovirus (ADV-Avi) via biotin-avidin interaction to deliver ADV specifically to EGF receptor over-expressing cancer cells. ADV-Avi/biotin-PEG-EGF complexes showed greatly enhanced intracellular uptake of ADV particles for an EGF receptor positive cell line (A431 cells), compared to naked or PEG alone immobilized ADV. ADV coding an exogenous GFP gene was used to quantitatively evaluate the level of GFP expression.

Development of a marine fish model for studying in vivo molecular responses in ecotoxicology.

A protocol for fixation and processing of whole adult marine medaka (Oryzias melastigma) was developed in parallel with in situ hybridization (ISH) and immunohistochemistry (IHC) for molecular analysis of in vivo gene and protein responses in fish. Over 200 serial sagittal sections (5microm) can be produced from a single adult medaka to facilitate simultaneous localization and quantification of gene-specific mRNAs and proteins in different tissues and subcellular compartments of a single fish. Stereological analysis (as measured by volume density, V(v)) was used to quantify ISH and IHC signals on tissue sections.

Chromatin, gene silencing and HIV latency.

One of the cellular defenses against virus infection is the silencing of viral gene expression. There is evidence that at least two gene-silencing mechanisms are used against the human immuno-deficiency virus (HIV). Paradoxically, this cellular defense mechanism contributes to viral latency and persistence, and we review here the relationship of viral latency to gene-silencing mechanisms.

Differential impact of aging and gender on lipid and lipoprotein profiles in a cohort of healthy Chinese Singaporeans.

Aim: To evaluate the impact of age and gender on lipid and lipoprotein profiles and the burden of dyslipidemia in a cohort of healthy Chinese Singaporean.

Methods: A total of 1 775 healthy Chinese, 536 men and 1 239 women aged between 30 and 70 years old were involved in the present study.

Results: Gender differences in all lipid and lipoprotein levels were clearly evident.

Differential proteome analysis of hagfish dental and somatic skeletal muscles.

Hagfish, the plesiomorphic sister group of all vertebrates, are deep-sea scavengers. The large musculus (m.) longitudinalis linguae (dental muscle) is a specialized element of the feeding apparatus that facilitates the efficient ingestion of food.

Curcumin effects on blood lipid profile in a 6-month human study.

Studies in animals and a short-term human study have suggested that curcumin, a polyphenolic compound concentrated in the curry spice turmeric, decreases serum cholesterol concentration. However, no controlled human trials have examined the effect of curcumin on cholesterol. This study investigated the effects of consuming curcumin on the serum lipid profile in men and women.

Microencapsulation of PEGylated adenovirus within PLGA microspheres for enhanced stability and gene transfection efficiency.

Purpose: Green fluorescent protein (GFP) encoding adenovirus (ADV) was surface modified with polyethylene glycol (PEG) for microencapsulation within poly(lactic-co-glycolic acid) (PLGA) microspheres with the aim of improving stability and gene transfection activity.

Methods: A series of PEGylated ADV (PEG-ADV) with different PEG seeding densities on the viral surface was prepared and the GFP expression efficiency of each PEG-ADV in the series determined. The physical stabilities of naked ADV and PEG-ADV were comparatively evaluated by exerting a high shear homogenization process or by exposure to low pH.

Venezuelan equine encephalitis virus replicon particles encoding respiratory syncytial virus surface glycoproteins induce protective mucosal responses in mice and cotton rats.

Respiratory syncytial virus (RSV) is an important viral pathogen that causes severe lower respiratory tract infection in infants, the elderly, and immunocompromised individuals. There are no licensed RSV vaccines to date. To prevent RSV infection, immune responses in both the upper and lower respiratory tracts are required.

Direct plasmid DNA encapsulation within PLGA nanospheres by single oil-in-water emulsion method.

Plasmid DNA was encapsulated within poly(d,l-lactic-co-glycolic acid) (PLGA) nanospheres by using polyethylene glycol (PEG) assisted solubilization technique of plasmid DNA in organic solvents. Plasmid DNA was solubilized in an organic solvent mixture composed of 80% methylene chloride and 20% DMSO by producing PEG/DNA nano-complexes having an average diameter less than 100 nm. DNA could be solubilized in the organic solvent mixture to a greater extent with increasing the weight ratio of PEG/DNA.

Polyethylene glycol modification of adenovirus reduces platelet activation, endothelial cell activation, and thrombocytopenia.

Thrombocytopenia is one of the complications for in vivo administration of adenovirus serotype 5 (Ad5) vectors after intravenous injection. In this paper, we investigated the mechanism of Ad5-induced thrombocytopenia and how these effects are attenuated by polyethylene glycol (PEG) modification of Ad5 (Ad-PEG). After intravenous injection, accelerated platelet loss was observed in Ad-injected mice but not in their Ad-PEG-injected counterparts.

Interactions among age, adiposity, bodyweight, lifestyle factors and sex steroid hormones in healthy Singaporean Chinese men.

Aim: To examine the inter-relationships among age, lifestyle factors, anthropometric parameters, percent body fat and steroid hormone parameters in 531 healthy Singaporean Chinese men aged between 29 and 72 years old.

Methods: Various lifestyle parameters were quantified through a survey, and testosterone (T), estradiol (E2), dehydroepiandrosterone sulphate (DHEAS) and sex hormone binding globulin (SHBG) were measured using established methods. Anthropometric parameters were collected and computed, and percent body fat (Siri) was measured using the DEXA scanner.

Antisense oligodeoxynucleotide-conjugated hyaluronic acid/protamine nanocomplexes for intracellular gene inhibition.

Green fluorescent protein (GFP) antisense oligodeoxynucleotide (ODN) was covalently conjugated to hyaluronic acid (HA) via a reducible disulfide linkage, and the HA-ODN conjugate was complexed with protamine to increase the extent of cellular uptake and enhance the gene inhibition efficiency of GFP expression. The HA-ODN conjugate formed more stable polyelectrolyte complexes with protamine as compared to naked ODN, probably because of its increased charge density. The higher cellular uptake of protamine/HA-ODN complexes than that of protamine/naked ODN complexes was attributed to the formation of more compact nanosized complexes (approximately 200 nm in diameter) in aqueous solution.

High-frequency whole-body vibration improves balancing ability in elderly women.

Objective: To investigate the efficacy of high-frequency whole-body vibration (WBV) on balancing ability in elderly women.

Design: Randomized controlled trial. Subjects were randomized to either the WBV intervention or the no-treatment control group.

Target-specific intracellular delivery of siRNA using degradable hyaluronic acid nanogels.

Novel hyaluronic acid (HA) nanogels physically encapsulating small interfering RNA (siRNA) were fabricated by an inverse water-in-oil emulsion method. Thiol-conjugated HA dissolved in aqueous emulsion droplets was ultrasonically crosslinked via the formation of disulfide linkages to produce HA nanogels with a size distribution from 200 to 500 nm. Green fluorescence protein (GFP) siRNA was physically entrapped within the HA nanogels during the emulsion/crosslinking process.

Stable gene expression occurs from a minority of integrated HIV-1-based vectors: transcriptional silencing is present in the majority.

Human immunodeficiency virus (HIV)-based vectors are being increasingly used in vitro for gene transfer and in vivo for gene therapy. The proportion of integrated retroviral vectors that are silenced or remain transcriptionally active, and the stability of gene expression in the latter remains poorly explored. To study this, T cells were infected with an HIV-1-based vector construct containing a long terminal repeat-driven reporter gene.

Sound characteristics of big-snout croaker, Johnius macrorhynus (Sciaenidae).

The sounds of a big-snout croaker, Johnius macrorhynus, produced under hand-held and voluntary conditions (in a large aquarium and in the field) were compared. Voluntary calls included "purr" and "dual-knocks", only purrs were produced when the fish was hand-held. The purr is composed of pulses in which the first interpulse interval was six to nine times longer than the other interpulse intervals, which were approximate in duration, and is a unique sound type in the coastal water of Taiwan.