Serum exosomal microRNAs as novel biomarkers for hepatocellular carcinoma

Recent studies have shown that circulating microRNAs are a potential biomarker in various types of malignancies. The aim of this study was to investigate the feasibility of using serum exosomal microRNAs as novel serological biomarkers for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We measured the serum exosomal microRNAs and serum circulating microRNAs in patients with CHB (n=20), liver cirrhosis (LC) (n=20) and HCC (n=20). Serum exosomal microRNA was extracted from 500 μl of serum using an Exosome RNA Isolation kit. The expression levels of microRNAs were quantified by real-time PCR. The expression levels of selected microRNAs were normalized to Caenorhabditis elegans microRNA (Cel-miR-39). The serum levels of exosomal miR-18a, miR-221, miR-222 and miR-224 were significantly higher in patients with HCC than those with CHB or LC (P<0.05). Further, the serum levels of exosomal miR-101, miR-106b, miR-122 and miR-195 were lower in patients with HCC than in patients with CHB (P=0.014, P<0.001, P<0.001 and P<0.001, respectively). There was no significant difference in the levels of miR-21 and miR-93 among the three groups. Additionally, the serum levels of circulating microRNAs showed a smaller difference between HCC and either CHB or LC. This study suggests that serum exosomal microRNAs may be used as novel serological biomarkers for HCC.     

Gold Nanorod–Photosensitizer Complex Obtained by Layer‐by‐Layer Method for Photodynamic/Photothermal Therapy In Vitro

Gold nanorod (GNR)–photosensitizer (PS) complex was prepared using anionic PS (sodium salt of purpurin‐18) and cationic poly(allylamine hydrochloride) by layer‐by‐layer method, and was characterized by transmission electron microscopy, UV‐vis spectroscopy, and zeta potential. The GNR–PS complex is a promising agent for synergistic (photothermal and photodynamic) therapy (PTT/PDT), in which PTT generates heat as well as operates the PS release which maximize the following PDT activity. The combined dual therapy, PTT followed by PDT, exhibits a significantly higher photocytotoxicity result based on synergistic effect of hyperthermia from PTT as well as singlet oxygen photogeneration from PDT.     

Determination of Bone Trabeculae Modulus—An Ultrasonic Scanning and MicroCT (μCT) Imaging Combination Approach

To date, there is no method to measure non-destructively the modulus of trabeculae within cancellous bone, whilst retaining its structural integrity. In this study ultrasonic scanning, coupled with microCT imaging, is employed to determine trabeculae modulus along the three major anatomical axes non-destructively. The proposed method allows cancellous bone specimens to remain intact, for possible use in subsequent studies. Volume rendering of the microCT images allows three-dimensional visualization of cancellous bone specimens to be tested. This facilitates trabeculae selection and accurate measurement of distance traveled by the ultrasonic wave, thus yielding a good degree of confidence in the acoustic velocity measured. For all the three principal anatomical directions, the measured acoustic speeds ranged from 2,115 to 3,077 m/s, giving an average of 2,505 m/s. Average wave velocities in the superior–inferior, medial–lateral and anterior–posterior anatomical directions were found to be 2,295, 2,469 and 2,754 m/s, respectively; the differences corresponding to the three directions do not appear to be significant. Subsequently, the modulus was then determined using elastic wave propagation theory.     

A Technique for Dynamic Tensile Testing of Human Cervical Spine Ligaments

An experimental study is undertaken to examine the dynamic stress–strain characteristics of ligaments from the human cervical spine (neck). Tests were conducted using a tensile split Hopkinson bar device and the engineering strain rates imposed were of the order of 10²∼10³/s. As ligaments are extremely soft and pliable, specialized test protocols applicable to Hopkinson bar testing were developed to facilitate acquisition of reliable and accurate data. Seven primary ligaments types from the cervical spines of three male cadavers were subjected to mechanical tests. These yielded dynamic stress–strain curves which could be approximated by empirical equations. The dynamic failure stress/load, failure stain/deformation, modulus/stiffness, as well as energy absorption capacity, were obtained for the various ligaments and classified according to their location, the strain rate imposed and the cadaveric source. Compared with static responses, the overall average dynamic stress–strain behavior foreach type of ligament exhibited an elevation in strength but reduced elongation.     

Simultaneous multiresidue determination of 48 pesticides in Yeongsan and Sumjin River water using GC-NPD and confirmation via GC-MS

In a continuation of our earlier work, a multiresidual analytical method using 48 frequently used neutral pesticides in a water matrix was developed and validated in this study. The samples were extracted with dichloromethane and the pesticides were analyzed via GC-NPD followed by confirmation with GC-MS. Good linearity was detected over a concentration range of 0.01-1.0 microg/mL with correlation coefficients (r(2) ) in excess of 0.982. The recoveries were measured between 70.7 and 111.4% for the majority of the targeted pesticides with relative standard deviations (RSDs) of less than 20%. The LODs and LOQs were in ranges of 0.1-2 and 0.33-6.6 microg/L, respectively. A total of 66 water samples were collected from different locations in Yeongsan and the Sumjin River, Republic of Korea, and were analyzed in accordance with the developed method. None of the water samples were determined to contain any of the targeted pesticides. The method has been shown to be simpler, faster, and more cost-effective than the method established by the Environmental Protection Agency (EPA).     

Synthesis of cuprous oxide nanocomposite electrodes by room-temperature chemical partial reduction

We demonstrate a template-free synthetic approach for the preparation of a highly conductive Cu/Cu(2)O nanocomposite electrode by a chemical reduction process. Cu(2)O octahedra were prepared through chemical dehydrogenation of as-synthesized Cu(OH)(2) nanowire precursors. To provide a sufficiently electron-conducting network, the Cu(2)O particles were transformed into Cu/Cu(2)O nanocomposites by an intentional reduction process. The Cu/Cu(2)O nanocomposite electrodes showed enhanced cycling performance compared to Cu(2)O particles. Furthermore, their rate capabilities were superior to those of their mechanically mixed Cu/Cu(2)O counterparts. This enhanced electrochemical performance of the hybrid Cu/Cu(2)O nanocomposites was ascribed to the formation of homogeneous nanostructures, offering an efficient electron-transport path provided by the presence of highly dispersed Cu nanoparticles.     

Formulation variation and in vitro-in vivo correlation for a rapidly swellable three-layered tablet of tamsulosin HCl

In order to develop a preferable once-a-day oral tablet formulation, various formulations of three-layered tablets containing tamsulosin HCl as a hydrophilic model drug were evaluated and compared with a commercial reference, tamsulosin OCAS?. When the test tablet was exposed to a release medium, the medium quickly permeated to the mid-layer and the two barrier layers swelled surrounding the mid-layer rapidly. Volume expansion showed faster and enough swelling of the three-layered tablet up to 2 h. Larger amount of barrier layers caused reduced release kinetics and a high molecular weight polymer showed more resistance against agitation force. A formulation with water-soluble mid-layer showed fast erosion decreasing its volume significantly. On the pharmacokinetic study, the mean ratio of area under the curve (AUC) and C(max) for the test formulation to the reference was 0.69 and 0.84, respectively, showing that the absorption of the drug was less complete than the reference. Plasma concentration at 24 h of the test formulation was higher than the reference. The Wagner-Nelson method showed that decreased initial dissolution rate might be the cause of the less complete absorption. On considering in vitro-in vivo correlation (IVIVC), level A, the reference (R2=0.981) showed more linear relationship than the test (R2=0.918) due to the decreased dissolution and absorption rate of the formulation. This result suggests that the in vitro dissolution profiles and release kinetics might be useful in correlating absorption kinetics as well as overall plasma drug concentration-time profiles for formulation studies.     

neo‐Clerodane Diterpenoids from the Aerial Part of Scutellaria barbata

Three new neo‐clerodane diterpenoids, barbatellarines C–E ( 1 – 3 ), were isolated from the CHCl₃‐soluble fraction of the aerial part of Scutellaria barbata. Their chemical structures were elucidated by detailed analysis of NMR and MS data. Compounds 1 and 2 were C(13) epimers, which was confirmed by an NOE difference experiment and the NOESY spectrum. The relative configuration was determined on the basis of the ¹H‐NMR J‐value and NOE data, while the absolute configuration of the previously isolated analogue, barbatellarine B ( 4 ), as a representative member of the group, was assigned by CD analysis.     

Common variants at the promoter region of the APOM confer a risk of rheumatoid arthritis

Although the genetic component in the etiology of rheumatoid arthritis (RA) has been consistently suggested, many novel genetic loci remain to uncover. To identify RA risk loci, we performed a genome-wide association study (GWAS) with 100 RA cases and 600 controls using Affymetrix SNP array 5.0. The candidate risk locus (APOM gene) was re-sequenced to discover novel promoter and coding variants in a group of the subjects. Replication was performed with the independent case-control set comprising of 578 RAs and 711 controls. Through GWAS, we identified a novel SNP associated with RA at the APOM gene in the MHC class III region on 6p21.33 (rs805297, odds ratio (OR) = 2.28, P = 5.20 × 10-7). Three more polymorphisms were identified at the promoter region of the APOM by the re-sequencing. For the replication, we genotyped the four SNP loci in the independent case-control set. The association of rs805297 identified by GWAS was successfully replicated (OR = 1.40, P = 6.65 × 10-5). The association became more significant in the combined analysis of discovery and replication sets (OR = 1.56, P = 2.73 × 10-10). The individuals with the rs805297 risk allele (A) at the promoter region showed a significantly lower level of APOM expression compared with those with the protective allele (C) homozygote. In the logistic regressions by the phenotype status, the homozygote risk genotype (A/A) consistently showed higher ORs than the heterozygote one (A/C) for the phenotype-positive RAs. These results indicate that APOM promoter polymorphisms are significantly associated with the susceptibility to RA.     

Alveolar macrophages modulate allergic inflammation in a murine model of asthma

The role of alveolar macrophages (AMs) in the pathogenesis of asthma is still unknown. The aim of the present study was to investigate the effects of AM in the murine model of asthma. AMs were selectively depleted by liposomes containing clodronate just before allergen challenges, and changes in inflammatory cells and cytokine concentrations in bronchoalveolar lavage (BAL) fluid were measured. AMs were then adoptively transferred to AM-depleted sensitized mice and changes were measured. Phenotypic changes in AMs were evaluated after in vitro allergen stimulation. AM-depletion after sensitization significantly increased the number of eosinophils and lymphocytes and the concentrations of IL-4, IL-5 and GM-CSF in BAL fluid. These changes were significantly ameliorated only by adoptive transfer of unsensitized AMs, not by sensitized AMs. In addition, in vitro allergen stimulation of AMs resulted in their gaining the ability to produce inflammatory cytokines, such as IL-1β, IL-6 and TNF-α, and losing the ability to suppress GM-CSF concentrations in BAL fluid. These findings suggested that AMs worked probably through GM-CSF-dependent mechanisms, although further confirmatory experiments are needed. Our results indicate that the role of AMs in the context of airway inflammation should be re-examined.