Enhancement of neurite outgrowth in PC12 cells by iron oxide nanoparticles

Despite the many potential therapeutic applications of iron oxide nanoparticle such as its use as an imaging and targeting tool, its biological effects have not yet been extensively characterized. Herein, we report that iron oxide nanoparticles taken up by PC12 cells can enhance neurite outgrowth. PC12 cells exposed to both iron oxide nanoparticles and nerve growth factor (NGF) synergistically increased the efficiency of neurite outgrowth in a dose-dependent manner. This may have resulted from the activation of cell adhesion molecules that are associated with cell-matrix interactions through iron. Immunoblotting assays also revealed that both neural specific marker protein and cell adhesion protein expression were upregulated by iron oxide nanoparticles compared with non-treated cells via activation of the mitogen-activated protein kinase (MAPK) signaling pathway. Our findings point to the possibility that iron oxide nanoparticles can affect cell-substrate interactions and regulate cell behaviors, which provides clinical insights into potential neurologic and therapeutic applications of iron oxide nanoparticles.     

Toxicogenomic comparison of multi-wall carbon nanotubes (MWCNTs) and asbestos

Carbon nanotubes (CNTs) have specific properties, including electrical and thermal conductivity, great strength, and rigidity, that allow them to be used in many fields. However, this increasing contact with humans and the environment is also raising health and safety concerns. Thus, research on the safety of CNTs has attracted much interest, including a comparison of the toxic effects of asbestos and carbon nanotubes, due to their physical similarity of a high aspect ratio (length/diameter). Nonetheless, there has not yet been a toxicogenomic comparison. Therefore, to examine toxicogenomic effects, the 50% growth inhibition (GI₅₀) concentration was determined for multi-wall carbon nanotubes (MWCNTs) and asbestos (crocidolite) and found to be approximately 0.0135 and 0.066%, respectively, in the case of 24-h treatment of normal human bronchial epithelia (NHBE) cells. Using these GI₅₀ concentrations, NHBE cells were then treated with MWCNTs and asbestos for 6 and 24 h, followed by a DNA microarray analysis. Among 31,647 genes, 1,201 and 1,252 were up-regulated by both asbestos and MWCNTs after 6 and 24 h of exposure, respectively. Meanwhile, 1,977 and 1,542 genes were down-regulated by both asbestos and MWNCTs after 6 and 24 h of exposure, respectively. In particular, the asbestos and MWCNTs both induced an over twofold up- and down-regulated expression of 12 mesothelioma-related genes and 22 lung cancer-related genes when compared with the negative control. Plus, the genes induced by the MWCNT exposure were expressed in the brain, lungs, epithelium, liver, and colon.     

Fabrication of drug-loaded polymer microparticles with arbitrary geometries using a piezoelectric inkjet printing system

Carrier geometry is a key parameter of drug delivery systems and has significant impact on the drug release rate and interaction with cells and tissues. Here we present a piezoelectric inkjet printing system as a simple and convenient approach for fabrication of drug-loaded polymer microparticles with well-defined and controlled shapes. The physical properties of paclitaxel (PTX)-loaded poly(lactic-co-glycolic acid) (PLGA) inks, such as volatility, viscosity and surface tension, were optimized for piezoelectric inkjet printing, and PTX-loaded PLGA microparticles were fabricated with various geometries, such as circles, grids, honeycombs, and rings. The resulting microparticles with 10% (w/w) PTX exhibited a fairly homogeneous shape and size. The microparticle fabrication by piezoelectric inkjet printing was precise, reproducible, and highly favorable for mass production. The microparticles exhibited a biphasic release profile with an initial burst due to diffusion and a subsequent, slow second phase due to degradation of PLGA. The release rate was dependent on the geometry, mainly the surface area, with a descending rate order of honeycomb>grid, ring>circle. The PTX-loaded microparticles showed a comparable activity in inhibiting the growth of HeLa cells. Our results demonstrate that a piezoelectric inkjet printing system would provide a new approach for large-scale manufacturing of drug carriers with a desired geometry.     

Construction of polyheterocyclic benzopyran library with diverse core skeletons through diversity-oriented synthesis pathway: part II

As a continuation of our previous report (J. Comb. Chem.2010, 12, 548-558), we accomplished the diversity-oriented synthesis of polyheterocyclic small-molecule library with privileged benzopyran substructure. To ensure the synthetic efficiency, we utilized the solid-phase parallel platform and the fluorous-tag-based solution-phase parallel platform to construct a 284-member polyheterocyclic library with six distinct core skeletons with an average purity of 87% on a scale of 5-10 mg. This library was designed to maximize the skeletal diversity with discrete core skeletons in three-dimensional space and the combinatorial diversity with four different benzopyranyl starting materials and various building blocks. Together with our reported benzopyranyl library, we completed the construction of polyheterocyclic benzopyran library with 11 unique scaffolds and their molecular diversity was visualized in chemical space using principle component analysis (PCA).     

Microalbuminuria in normal Korean children

Purpose

Although microalbuminuria is known as a predictor of clinical nephropathy and cardiomyopathy, few studies have investigated the incidence and reference range of microalbuminuria in healthy children. This study aimed to establish a reference range and to study the age-related trend for spot urine microalbumin/creatinine ratio in a Korean pediatric population.

Materials and Methods

352 healthy children were studied from July 2007 through March 2010. Height, weight, serum creatinine, spot urine microalbumin/creatinine ratio, and glomerular filtration rate (GFR) were obtained for each subject. We divided the study population into 5 groups according to age, and compared the spot urine microalbumin/creatinine ratio with other variables using one-way analysis of variance (ANOVA), regression analysis and Pearson''s correlation analysis.

Results

In this study, the data showed that the spot urine microalbumin/creatinine ratio decreased with age: 1-12 months, 22.72±13.80 mg/mmol (2SD: 3.33-54.40 mg/mmol); 13-28 months, 16.34±9.58 mg/mmol (2SD: 3.16-35.19 mg/mmol); 29-48 months, 13.12±9.74 mg/mmol (2SD: 3.01-41.57 mg/mmol); 4-6 years, 10.58±8.13 mg/mmol (2SD: 0.00-30.19 mg/mmol); and 7-19 years, 5.13±5.44 mg/mmol (2SD: 0.45-14.45 mg/mmol). The spot urine microalbumin/creatinine ratio showed correlation with age, height, height z-score, weight, weight z-score, GFR, body mass index (BMI) and body surface area (BSA).

Conclusion

The spot urine microalbumin/creatinine ratio in normal Korean children decreased with age. This ratio could potentially be used to establish reference ranges and cutoff values for Korean children and to predict nephropathy and cardiomyopathy.     

Association of the adiponectin gene variations with risk of ischemic stroke in a Korean population

Purpose

Stroke is the second leading cause of death and a major cause of morbidity and mortality worldwide. Evidence of variations in adiponectin(AdipoQ) genes that are associated with ischemic stroke has not been consistent, and it is unclear whether the same loci contribute to these associations in the Korean population. Using a Korean population, we tested ischemic stroke-associated AdipoQ markers.

Materials and Methods

In a preliminary genome-wide association study using 320 250 k Affymetrix NSP chips, AdipoQ was found to be associated with ischemic stroke in Koreans. To study of AdipoQ, a further 673 ischemic stroke patients and 267 unrelated individuals without a history of stroke or transient ischemic attack were examined in a case-control study.

Results

Six polymorphisms (rs182052G > A, rs16861205G > A, rs822391T > C, rs822396A > G, rs12495941G > T and rs3774261A > G) that had a minor allele frequency of over 1% were strongly associated with stroke (p < 0.05). Two of these, rs822391T > C and rs822396A > G showed this association on both dominant and additive logistic regression analysis after adjusting for age and sex. The haplotypes ht 1 (AGGCGG and AAGTAG) were significantly associated with susceptibility to stroke.

Conclusion

Our findings show that polymorphisms in AdipoQ are associated with risk for ischemic stroke in the Korean population. This study lends further support to the putative role of AdipoQ in stroke.     

Soluble human leukocyte antigen G level in fluid from single dominant follicle and the association with oocyte competence

Purpose

To investigate the direct relationship between the follicular fluid (FF) level of soluble human leukocyte antigen G (HLA-G) and fertilizability of the corresponding oocyte as well as the morphological quality of the corresponding embryo.

Materials and Methods

Sixty-three patients were stimulated with recombinant FSH combined with gonadotropin-releasing hormone (GnRH) agonist long (n=5) or antagonist protocol (n=58) for standard in vitro fertilization (IVF). At the time oocyte retrieval, follicular fluid was obtained from single dominant follicle in 63 patients, and the level of soluble HLA-G was measured by sandwich enzyme-liked immunosorbent assay (ELISA). Normal fertilization and individual embryo quality were evaluated, and were graded to four categories by morphological criteria (the embryo with symmetrical blastomeres and no fragmentation were assigned as grade A). Good-quality embryo was defined as those with grade A or B.

Results

Soluble HLA-G was not detected in 15 FF samples. In the group with positive FF soluble HLA-G (sHLA-G) (n=48), high levels of sHLA-G (>117.758 U/mL) could predict the failure of fertilization with statistical significance {area under the curve (AUC) 0.676, 95% confidence interval (CI) 0.525-0.804}. However, the FF sHLA-G level was not related with the formation of good-quality embryo.

Conclusion

High level of FF sHLA-G could predict the fertilization failure of the corresponding oocyte, but was not related with the formation of good-quality embryo.     

Prostate cancer with solitary metastases to the bilateral testis

We present the case of an 81-year-old patient with testicular metastasis from prostate carcinoma. After the initial diagnosis of prostate cancer, he had an 8-year course of hormonal therapy and showed no clinical evidence of metastasis to other organs. Asymptomatic metastasis of prostate carcinoma to the testis is a rare clinical condition. We diagnosed his condition, based on histopathology following a subcapsular orchiectomy and transurethral resection of the prostate.