[Expression of Glucose Transporter 1 in Human Laryngeal Squamous Cell Carcinoma and Its Clinical Significance]

Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi = Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery. Dec, 2010  |  Pubmed ID: 21395180

To investigate the expression of glucose transporter 1 (GLUT1) in human laryngeal squamous cell carcinoma and its relationship to clinical pathologic factors.

Development of Microsatellite Loci for the Invasive Weed Wedelia Trilobata (Asteraceae)

American Journal of Botany. Nov, 2010  |  Pubmed ID: 21616811

• Premise of the study: Microsatellite markers were developed to help elucidate the population genetics of the invasive species Wedelia trilobata. • Methods and Results: Using the Fast Isolation by AFLP of Sequences COntaining (FIASCO) repeats protocol, 23 sets of primers for amplifying microsatellite loci were identified in W. trilobata, 10 of which showed polymorphism (two to five alleles per locus) in samples of two populations of W. trilobata, one from China and one from Peru. Six of these loci were successfully amplified from samples of the native congener W. chinensis, with expected sizes. • Conclusions: These markers may be useful for further investigation of population genetics of Wedelia trilobata and other congener species.

An Integrated Analysis of the Efficacy of Fluticasone Furoate Nasal Spray on Individual Nasal and Ocular Symptoms of Seasonal Allergic Rhinitis

Allergy and Asthma Proceedings : the Official Journal of Regional and State Allergy Societies. Nov-Dec, 2010  |  Pubmed ID: 21708060

Intranasal steroids have been shown to affect ocular symptoms of allergic rhinitis (AR). The results of the published literature, however, are not uniform across all products. This study was designed to evaluate whether the effects of fluticasone furoate nasal spray (FFNS) are consistent across different allergy seasons and different geographic regions for individual nasal and ocular symptoms of seasonal allergic rhinitis (SAR). An integrated analysis was performed on data from four randomized, double-blind, placebo-controlled, parallel-group, multicenter trials, designed to evaluate the efficacy and safety of FFNS, 110 micrograms, once daily for 14 days in 1141 adult and adolescent SAR patients exposed to mountain cedar, ragweed, or grass pollen allergen. All patients evaluated severity of seven individual nasal and ocular symptoms on a 4-point categorical scale. The main efficacy measures included change from baseline in daily reflective, morning (A.M.) predose instantaneous, and daily A.M. and evening (P.M.) reflective score for each nasal/ocular symptom. FFNS significantly improved daily mean reflective, A.M. predose instantaneous, and daily A.M. and P.M. reflective scores for nasal itching, sneezing, congestion, rhinorrhea, and ocular itching/burning, tearing/watering, and redness, compared with placebo (p < 0.001 for all versus placebo). The least square (LS) mean treatment differences ranged from -0.44 to -0.33 (p < 0.0001) for the individual nasal symptoms and from -0.22 to -0.19 (p < 0.0001) for the individual ocular symptoms. FFNS also significantly improved daily reflective total nasal symptom scores (TNSS)/reflective total ocular symptom scores (TOSS), and A.M. predose instantaneous TNSS and instantaneous TOSS, compared with placebo (LS mean treatment differences = -1.47, -0.65, -1.49, and -0.63, respectively; p < 0.001 for all). FFNS, 110 micrograms, once daily consistently relieved all nasal and ocular symptoms of SAR across different allergy seasons and geographical locations.

Preparation and Characterization of Spindle-like Fe3O4 Mesoporous Nanoparticles

Nanoscale Research Letters. 2011  |  Pubmed ID: 21711591

ABSTRACT: Magnetic spindle-like Fe3O4 mesoporous nanoparticles with a length of 200 nm and diameter of 60 nm were successfully synthesized by reducing the spindle-like α-Fe2O3 NPs which were prepared by forced hydrolysis method. The obtained samples were characterized by transmission electron microscopy, powder X-ray diffraction, attenuated total reflection fourier transform infrared spectroscopy, field emission scanning electron microscopy, vibrating sample magnetometer, and nitrogen adsorption-desorption analysis techniques. The results show that α-Fe2O3 phase transformed into Fe3O4 phase after annealing in hydrogen atmosphere at 350°C. The as-prepared spindle-like Fe3O4 mesoporous NPs possess high Brunauer-Emmett-Teller (BET) surface area up to ca. 7.9 m2 g-1. In addition, the Fe3O4 NPs present higher saturation magnetization (85.2 emu g-1) and excellent magnetic response behaviors, which have great potential applications in magnetic separation technology.

[Distribution Patterns of PAHs in Soils from Coking Plant and the Particle-size Cut Points of Soil Washing]

Huan Jing Ke Xue= Huanjing Kexue / [bian Ji, Zhongguo Ke Xue Yuan Huan Jing Ke Xue Wei Yuan Hui "Huan Jing Ke Xue" Bian Ji Wei Yuan Hui.]. Apr, 2011  |  Pubmed ID: 21717762

Soil particle size distribution and contaminants distribution patterns in different soil size fractions are the basis of soil treatability using soil washing method. Soil particle-size cut points are important parameters of soil washing process. According to ex situ soil washing technology, soil samples were collected in a former coking plant. The soil particle size distribution and the concentrations of 16 polycyclic aromatic hydrocarbons (PAHs) in USEPA priority list were analyzed. Tween 80 and Triton X-100 solutions were used to clean the polluted soil with different particle size. Results showed that the total concentrations of 16 PAHs ranged from 6.27 to 40.18 mg/kg dry weight in the six soil size fractions and present a bimodal distribution. The maximum individual PAH concentration mostly occurred in the 250-500 microm size fraction. The lowest individual PAH concentration was in the 50-75 microm size fraction. The removal efficiencies of PAHs in different soil size fractions depended on their initial concentrations and the characteristics of soil. The PAHs removal efficiencies in coarser size fractions were lower than that in the finer size fractions owing to their higher organic carbon content. Based on the removal efficiency of PAHs in each soil size fractions by surfactant solution and the requirements of waste volume reduction, 50 microm was determined as the particle-size cut point. Then, 82.95% volume reduction can be achieved.

Enhanced Oral Bioavailability of Cyclosporine A by Liposomes Containing a Bile Salt

International Journal of Nanomedicine. 2011  |  Pubmed ID: 21720508

The main purpose of this study was to evaluate liposomes containing a bile salt, sodium deoxycholate (SDC), as oral drug delivery systems to enhance the oral bioavailability of the poorly water-soluble and poorly permeable drug, cyclosporine A (CyA). Liposomes composed of soybean phosphatidylcholine (SPC) and SDC were prepared by a thin-film dispersion method followed by homogenization. Several properties of the liposomes including particle size, polydispersity index, and entrapment efficiency were characterized. The in vitro release of CyA from these liposomes was less than 5% at 12 hours as measured by a dynamic dialysis method. The pharmacokinetic results in rats showed improved absorption of CyA in SPC/SDC liposomes, compared with CyA-loaded conventional SPC/cholesterol (Chol) liposomes and microemulsion-based Sandimmune Neoral(®). The relative oral bioavailability of CyA-loaded SPC/SDC and SPC/Chol liposomes was 120.3% and 98.6%, respectively, with Sandimmun Neoral as the reference. The enhanced bioavailability of CyA was probably due to facilitated absorption by the liposomes containing SDC rather than improved release rate.

Enhanced Effect and Mechanism of Water-in-oil Microemulsion As an Oral Delivery System of Hydroxysafflor Yellow A

International Journal of Nanomedicine. 2011  |  Pubmed ID: 21720510

A microemulsion is an effective formulation for improving the oral bioavailability of poorly soluble drugs. In this paper, a water-in-oil (w/o) microemulsion was investigated as a system for enhancing the oral bioavailability of Biopharmaceutic Classification System (BCS) III drugs.

A Genome-wide Association Study Identifies Two New Lung Cancer Susceptibility Loci at 13q12.12 and 22q12.2 in Han Chinese

Nature Genetics. Aug, 2011  |  Pubmed ID: 21725308

Lung cancer is the leading cause of cancer-related deaths worldwide. To identify genetic factors that modify the risk of lung cancer in individuals of Chinese ancestry, we performed a genome-wide association scan in 5,408 subjects (2,331 individuals with lung cancer (cases) and 3,077 controls) followed by a two-stage validation among 12,722 subjects (6,313 cases and 6,409 controls). The combined analyses identified six well-replicated SNPs with independent effects and significant lung cancer associations (P < 5.0 × 10(-8)) located in TP63 (rs4488809 at 3q28, P = 7.2 × 10(-26)), TERT-CLPTM1L (rs465498 and rs2736100 at 5p15.33, P = 1.2 × 10(-20) and P = 1.0 × 10(-27), respectively), MIPEP-TNFRSF19 (rs753955 at 13q12.12, P = 1.5 × 10(-12)) and MTMR3-HORMAD2-LIF (rs17728461 and rs36600 at 22q12.2, P = 1.1 × 10(-11) and P = 6.2 × 10(-13), respectively). Two of these loci (13q12.12 and 22q12.2) were newly identified in the Chinese population. These results suggest that genetic variants in 3q28, 5p15.33, 13q12.12 and 22q12.2 may contribute to the susceptibility of lung cancer in Han Chinese.

Molecular Cloning, Polymorphism and Tissue Distribution of the MHC Class IIB Gene in the Chinese Goose (Anser Cygnoides)

British Poultry Science. Jun, 2011  |  Pubmed ID: 21732877

1. The goose major histocompatibility complex (MHC) class IIB cDNA (Ancy-MHCII) was cloned by homology cloning and rapid amplification of cDNA ends by polymerase chain reaction (RACE-PCR), and the genomic structure and tissue expression were investigated. 2. Three different 5'-RACE sequences (Ancy-MHC II5'-1, Ancy-MHC II5'-2, Ancy-MHC II5'-3), one 3'-RACE sequence (Ancy-MHC II-3') and two different full length Ancy-MHC IIB cDNA sequences (Ancy-CD01, Ancy-CD02), which came from different alleles at one locus or different loci, were determined. 3. The genomic organisation is composed of 6 exons and 5 introns, with a longer intron region than that of the chicken. The alleles encode 259 and 260 amino acids in the mature protein. 4. The number of non-synonymous substitutions (dN) in the peptide-binding region of exon 2 from 8 alleles was higher than that of the synonymous substitutions (dS). 5. Tissue-specific expression of Ancy-MHC II mRNA was detected in an adult goose using RT-PCR. These results showed that Ancy-MHC II mRNA was expressed in the lung, spleen, liver, intestine, heart, kidney, pancreas, brain, skin and muscle. This is consistent with the expression of MHC class IIB in various tissues from the chicken. 6. Sequences from goose, snipe and duck clustered together when compared with known MHC class IIB sequences from the other species, significantly differing from mammals and aquatic species, indicating a pattern consistent with accepted evolutionary pathways.

Controlled Synthesis of Monodisperse Sub-100 Nm Hollow SnO2 Nanospheres: a Template- and Surfactant-free Solution-phase Route, the Growth Mechanism, Optical Properties, and Application As a Photocatalyst

Chemistry (Weinheim an Der Bergstrasse, Germany). Aug, 2011  |  Pubmed ID: 21735499

Controlled synthesis of low-dimensional materials, such as nanoparticles, nanorods, and hollow nanospheres, is vitally important for achieving desired properties and fabricating functional devices. We report a systematic investigation of the growth of low-dimensional sub-100 nm SnO(2) hollow nanostructures by a mild template- and surfactant-free hydrothermal route, aiming to achieve precise control of morphology and size. The starting materials are potassium stannate and urea in an ethylene glycol (EG)/H(2)O system. We found the size of the SnO(2) hollow nanospheres can be controlled by simply adjusting the urea concentration. Investigation of the mechanism of formation of the SnO(2) hollow nanospheres revealed that reaction time, urea concentration, and reaction temperature make significant contributions to the growth of hollow nanospheres. On switching the solvent from EG/H(2)O to H(2)O or ethanol, the SnO(2) nanostructures changed from nanospheres to ultrafine nanorods and nanoparticles. On the basis of reaction parameter dependent experiments, oriented self-assembly and subsequent evacuation through Ostwald ripening are proposed to explain the formation of hollow nanostructures. Their size-dependent optical properties, including UV/Vis absorption spectra and room-temperature fluorescence spectra, were also studied. Moreover, the studies on the photocatalytic property demonstrate that the fabricated hollow structures have slightly enhanced photocatalytic degradation activity for rhodamine B when exposed to mercury light irradiation compared to solid SnO(2) nanospheres under the same conditions. The synthesized tin oxide nanoparticles display high photocatalytic efficiency and have potential applications for cleaning polluted water in the textile industry.

Blueberry Anthocyanins: Protection Against Ageing and Light-induced Damage in Retinal Pigment Epithelial Cells

The British Journal of Nutrition. Oct, 2011  |  Pubmed ID: 22018225

Retinal pigment epithelium (RPE) cells are vital for retinal health. However, they are susceptible to injury with ageing and exposure to excessive light, including UV (100-380 nm) and visible (380-760 nm) radiation. To evaluate the protective effect of blueberry anthocyanins on RPE cells, in vitro cell models of replicative senescent and light-induced damage were established in the present study. After purification and fractionation, blueberry anthocyanin extracts (BAE) were yielded with total anthocyanin contents of 31·0 (sd 0·5) % and were used in this study. Replicative senescence of RPE cells was induced by repeatedly passaging cells from the fourth passage to the tenth. From the fifth passage, cultured RPE cells began to enter a replicative senescence, exhibiting reduced cell proliferation along with an increase in the number of β-galactosidase-positive cells. RPE cells maintained high cell viability (P < 0·01) and a low (P < 0·01) percentage of β-galactosidase-positive cells when treated with 0·1 μg/ml BAE. In contrast, after exposure to 2500 (sd 500) lx light (420-800 nm) for 12 h, RPE cells in the positive control (light exposure, no BAE treatment) exhibited premature senescence, low (P < 0·01) cell viability and increased (P < 0·01) vascular endothelial growth factor (VEGF) release compared with negative control cells, which were not subjected to light irradiation and BAE exposure. Correspondingly, BAE is beneficial to RPE cells by protecting these cells against light-induced damage through the suppression of ageing and apoptosis as well as the down-regulation of the over-expressed VEGF to normal level. These results demonstrate that BAE is efficacious against senescence and light-induced damage of RPE cells.

Therapeutic Potential of Nrf2 Activators in Streptozotocin-induced Diabetic Nephropathy

Diabetes. Nov, 2011  |  Pubmed ID: 22025779

To determine whether dietary compounds targeting NFE2-related factor 2 (Nrf2) activation can be used to attenuate renal damage and preserve renal function during the course of streptozotocin (STZ)-induced diabetic nephropathy.

Simple and Sensitive Method for Detecting Point Mutations of Epidermal Growth Factor Receptor Using Cationic Conjugated Polymers

ACS Applied Materials & Interfaces. Nov, 2011  |  Pubmed ID: 22026576

The L858R mutation of epidermal growth factor receptor (EGFR) in nonsmall cell lung cancer is associated with the increased sensitivity to EGFR tyrosine kinase inhibitors. In this paper, a simple and sensitive method for identification of L858R mutation in cell lines and tumor tissues was developed using cationic conjugated polymer-based fluorescence resonance energy transfer technology (CCP-based FRET). The new detection system can detect even as low as 4-8% mutation of the total DNA. Through the detection results for 48 DNA samples from tumor tissues, a sensitivity of 95.24% (20/21) and a specificity of 96.30% (26/27) were demonstrated. Further, the application of this method in clinical molecular diagnosis was validated by detecting T790 M in EGFR of 35 patients. In comparison with DNA sequencing and real-time PCR methods, our new protocol simplifies procedures by eliminating the need for primer labeling, cumbersome workups and sophisticated instruments and improves sensitivity by amplifying fluorescence signals. Our CCP-based FRET technology is particularly attractive because of its higher sensitivity, cost-effective, and simple characteristics. Particularly, this new method could confirm the suspected positive samples arisen by DNA sequencing and real-time PCR methods. Thus, the CCP-based FRET technology opens up an avenue for clinical therapy by guiding medication to lung cancer patients responsive to anti-EGFR therapy.

[Conductive Keratoplasty for Presbyopia and Two Years Follow-up]

[Zhonghua Yan Ke Za Zhi] Chinese Journal of Ophthalmology. Jul, 2011  |  Pubmed ID: 22041486

To investigate the effect of conductive keratoplasty (CK) for presbyopia and 2 years follow-up.

Hollow Mesoporous Zeolite Microspheres: Hierarchical Macro-/meso-/microporous Structure and Exceptionally Enhanced Adsorption Properties

Dalton Transactions (Cambridge, England : 2003). Dec, 2011  |  Pubmed ID: 22041854

We report the synthesis of a new kind of uniform hollow zeolite microspheres with hierarchical macro-/meso-/microporosity by an efficient strategy combining bi-templating, steam-assisted crystallization and then a mild alkaline etching method. This novel product has a hollow architecture, highly crystallized zeolite shells and more importantly, high dye adsorption capabilities.

Financing Development Stage Biotechnology Companies: RMs Vs. IPOs

Journal of Health Care Finance. 2011  |  Pubmed ID: 22043645

We examine reverse mergers (RMs) in the biotechnology industry and find that, when compared to initial public offerings (IPOs), RMs are smaller, have significantly lower market valuations relative to size, and generally invest less. We also find that RMs exhibit positive abnormal returns on the announcement date and throughout the first year after the RM event. In looking at liquidity measures, we find that RMs tend to be less liquid than IPOs and that illiquidity is greater during the six-month lock-up period following the RM event. Thus, RMs may be an appropriate alternative financing vehicle in capital intensive, high-risk biotechnology companies which require accessing deeper and larger pools of investors in public capital markets across multiple milestone periods in a "pay for progress" environment.

[Origin and Evolution of Canine Parvovirus--a Review]

Wei Sheng Wu Xue Bao = Acta Microbiologica Sinica. Jul, 2011  |  Pubmed ID: 22043787

Canine parvovirus (CPV-2), first recognized in 1978 as a new pathogen of dogs, was probably derived from a very closely related virus in cats, feline panleukopaenia virus (FPLV) or a closely related carnivore parvovirus (FPLV-like virus). CPV-2 is responsible for either myocarditis or fatal gastroenteritis in pups with high morbidity and mortality. Shortly after its emergence, CPV-2 has become endemic in the global dog population. The original CPV-2 continued to evolve, and was subsequently replaced by three different but closely related antigenic variants, designated CPV-2a, CPV-2b and CPV-2c, which now coexist in dog populations worldwide. The genetic and antigenic variation in CPV-2 also correlated with changes in the host range and tissue tropisms of the virus. Here, we reviewed variation and evolution of CPV-2 in past 30 years and discussed CPV-2 as an important model to study virus evolution.

MiR-223 Suppresses Cell Proliferation by Targeting IGF-1R

PloS One. 2011  |  Pubmed ID: 22073238

To study the roles of microRNA-223 (miR-223) in regulation of cell growth, we established a miR-223 over-expression model in HeLa cells infected with miR-223 by Lentivirus pLL3.7 system. We observed in this model that miR-223 significantly suppressed the proliferation, growth rate, colony formation of HeLa cells in vitro, and in vivo tumorigenicity or tumor formation in nude mice. To investigate the mechanisms involved, we scanned and examined the potential and putative target molecules of miR-223 by informatics, quantitative PCR and Western blot, and found that insulin-like growth factor-1 receptor (IGF-1R) was the functional target of miR-223 inhibition of cell proliferation. Targeting IGF-1R by miR-223 was not only seen in HeLa cells, but also in leukemia and hepatoma cells. The downstream pathway, Akt/mTOR/p70S6K, to which the signal was mediated by IGF-1R, was inhibited as well. The relative luciferase activity of the reporter containing wild-type 3'UTR(3'untranslated region) of IGF-1R was significantly suppressed, but the mutant not. Silence of IGF-1R expression by vector-based short hairpin RNA resulted in the similar inhibition with miR-223. Contrarily, rescued IGF-1R expression in the cells that over-expressed miR-223, reversed the inhibition caused by miR-223 via introducing IGF-1R cDNA that didn't contain the 3'UTR. Meanwhile, we also noted that miR-223 targeted Rasa1, but the downstream molecules mediated by Rasa1 was neither targeted nor regulated. Therefore we believed that IGF-1R was the functional target for miR-223 suppression of cell proliferation and its downstream PI3K/Akt/mTOR/p70S6K pathway suppressed by miR-223 was by targeting IGF-1R.

80-MHz Intravascular Ultrasound Transducer Using PMN-PT Free-standing Film

IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control. Nov, 2011  |  Pubmed ID: 22083761

[Pb(Mg(1/3)Nb(2/3))O(3)](0.63)[PbTiO(3)](0.37) (PMN-PT) free-standing film of comparable piezoelectric properties to bulk material with thickness of 30 μm has been fabricated using a modified precursor coating approach. At 1 kHz, the dielectric permittivity and loss were 4364 and 0.033, respectively. The remnant polarization and coercive field were 28 μC/cm(2) and 18.43 kV/cm. The electromechanical coupling coefficient k(t) was measured to be 0.55, which was close to that of bulk PMN-PT single-crystal material. Based on this film, high-frequency (82 MHz) miniature ultrasonic transducers were fabricated with 65% bandwidth and 23 dB insertion loss. Axial and lateral resolutions were determined to be as high as 35 and 176 μm. In vitro intravascular imaging on healthy rabbit aorta was performed using the thin film transducers. In comparison with a 35-MHz IVUS transducer, the 80-MHz transducer showed superior resolution and contrast with satisfactory penetration depth. The imaging results suggest that PMN-PT free-standing thin film technology is a feasible and efficient way to fabricate very-high-frequency ultrasonic transducers.

Genetic and Virulence Characterization of Streptococcus Suis Type 2 Isolates from Swine in the Provinces of Zhejiang and Henan, China

Folia Microbiologica. Nov, 2011  |  Pubmed ID: 22083785

This study was aimed to examine the genetic characteristics of 44 Streptococcus suis type 2 (SS2) isolates and the virulence attributes of 23 representative isolates. Multilocus sequence typing revealed five sequence types (ST1, ST7, ST28, ST86, and ST162) with 19 isolates assigned to ST7 (43.2%), 14 to ST1 (31.8%), and 9 to ST28 (20.5%). PCR typing of the pilus gene clusters classified the isolates into three types: A (72.7%), B (22.7%), and N (4.5%). All isolates of pilus types A and N were assigned to the ST1 complex containing ST1, ST7, and ST86, while those of type B belonged to the ST27 complex comprising ST28 and ST162. Only two strains had the putative pathogenicity island 89-kb cluster (89K) and were of type N. The type B strains had a significantly lower adhesion, were more readily killed by macrophage, and had lower virulence to mice than those of types A and N. We conclude that SS2 strains of both ST1 and ST27 complexes, parallel to pilus types A and B, were prevalent in the pig populations in Zhejiang Province, and ST7 and ST1 strains were the predominant genotypes in the diseased pigs with pneumonia.

Hierarchical Mesoporous Zeolites: Direct Self-assembly Synthesis in a Conventional Surfactant Solution by Kinetic Control over the Zeolite Seed Formation

Chemistry (Weinheim an Der Bergstrasse, Germany). Dec, 2011  |  Pubmed ID: 22084015

By kinetic control over the zeolite seed formation, we report the direct fabrication of hierarchical mesoporous zeolites using hexadecyl trimethyl ammonium bromide (CTAB) as the soft template in a conventional solution route. Nanometer-sized, subnanocrystal-type zeolite seeds with a high degree of polymerization are essential to prevent the formation of a separate amorphous mesoporous phase and the phase separation between the mesophase and zeolite crystals in the presence of CTAB and a certain amount of ethanol. The mechanisms for the formation of hierarchically porous zeolites in the solution process, including the effect of mother liquid aging, formation of subnanocrystal zeolite seeds and their self-assembly effect with CTAB, and the role of ethanol are proposed and discussed in detail. The prepared mesoporous ZSM-5 zeolite showed much higher catalytic activity than conventional counterparts for aldol condensations involving large molecules, especially in the synthesis of vesidryl.

Intrahepatic Biliary Injuries Associated with Radiofrequency Ablation of Hepatic Malignancies

Chinese Medical Journal. Jul, 2011  |  Pubmed ID: 22088453

Biliary injury after radiofrequency ablation can cause serious consequences including death. However, there are limited data regarding bile duct changes with or without complications associated with radiofrequency ablation of hepatic malignancies. This study aimed to assess the incidence, prognosis and risk factors of intrahepatic biliary injury associated with radiofrequency ablation.

Clinical Utility of Automated Platelet Clump Count in the Screening for Ethylene Diamine Tetraacetic Acid-dependent Pseudothrombocytopenia

Chinese Medical Journal. Oct, 2011  |  Pubmed ID: 22088534

Platelet (PLT) clumping occurring in pseudothrombocytopenia (PTCP) can result in inaccurate PLT. Automated platelet clump count (APCC) is a quantitative parameter of platelet aggregation. In this study, we evaluated the clinical utility of APCC in the screening for platelet aggregation related ethylene diamine tetraacetic acid (EDTA)-dependent PTCP (EDTA-PTCP).

[Effects of Simvastatin Plus All-trans Retinoic Acid on WT1/hDMP1 Gene Expression Profiles of Human Promyelocytic Leukemia Cell Line NB4]

Zhonghua Yi Xue Za Zhi. Jul, 2011  |  Pubmed ID: 22093791

To investigate the effects of simvastatin (SV) plus all-trans retinoic acid (ATRA) on the proliferation, differentiation, apoptosis and WT1/hDMP1 gene expression profiles of human promyelocytic leukemia cell line NB4.

Early Protective Effect of Mitofusion 2 Overexpression in STZ-induced Diabetic Rat Kidney

Endocrine. Nov, 2011  |  Pubmed ID: 22095488

Diabetic nephropathy (DN) is a serious complication of diabetes with a poorly defined etiology and limited treatment options. Early intervention is key to preventing the progression of DN. Mitofusin 2 (Mfn2) regulates mitochondrial morphology and signaling, and is involved in the pathogenesis of numerous diseases. Furthermore, Mfn2 is also closely associated with the development of diabetes, but its functional roles in the diabetic kidney remain unknown. This study investigated the effect of Mfn2 at an early stage of DN. Mfn2 was overexpressed by adenovirus-mediated gene transfer in streptozotocin-induced diabetic rats. Clinical parameters (proteinuria, albumin/creatinine ratio), pathological changes, ultra-microstructural changes in nephrons, expression of collagen IV and phosph-p38, ROS production, mitochondrial function, and apoptosis were evaluated and compared with diabetic rats expressing control levels of Mfn2. Endogenous Mfn2 expression decreased with time in DN. Compared to the blank transfection control group, overexpression of Mfn2 decreased kidney weight relative to body weight, reduced proteinuria and ACR, and improved pathological changes typical of the diabetic kidney, like enlargement of glomeruli, accumulation of ECM, and thickening of the basement membrane. In addition, Mfn2 overexpression inhibited activation of p38, and the accumulation of ROS; prevented mitochondrial dysfunction; and reduced the synthesis of collagen IV, but did not affect apoptosis of kidney cells. This study demonstrates that Mfn2 overexpression can attenuate pathological changes in the kidneys of diabetic rats. Further studies are needed to clarify the underlying mechanism of this protective function. Mfn2 might be a potential therapeutic target for the treatment of early stage DN.

Effects of Subcutaneous Low Molecular Weight Heparin and Intravenous Unfractionated Heparin on Serum S100 Concentrations in Patients with Cerebrovascular Diseases

Clinical Chemistry and Laboratory Medicine : CCLM / FESCC. Nov, 2011  |  Pubmed ID: 22098432

Abstract Background: S100 plays an important role in diagnosis and prognosis of acute ischemic stroke. The objective was to investigate the effects of clinical heparins administrations on serum S100 concentrations in patients with cerebrovascular diseases. Methods: Forty cases were enrolled in this study, including 10 patients with percutaneous carotid intervention receiving intravenous unfractionated heparin (UFH) at the beginning of stenting (group A1), 10 patients with carotid angiography receiving UFH-free therapy (group A2), 10 patients with cerebral infarction receiving subcutaneous low molecular weight heparin (LMWH) anticoagulation therapy (group B1) and 10 patients with cerebral infarction receiving LMWH-free therapy (group B2). S100 concentrations were analyzed before and after heparin administrations. Results: A rapid increase of serum S100 (median, 1.74-fold, p<0.05) was observed in group A1 within 15 min of UFH administration. In group B1, S100 significantly increased (median, 1.44-fold, p<0.05) at 3 h after LMWH injection. Conclusions: Both intravenous UFH and subcutaneous LMWH administration induced increases in serum S100 concentrations. It should be taken into account when using S100 as a biomarker of cerebrovascular diseases.

Janus Kinase 3: the Controller and the Controlled

Acta Biochimica Et Biophysica Sinica. Nov, 2011  |  Pubmed ID: 22130498

Janus kinase (JAK)-signal transducer and activators of transcription (STAT) signaling pathways play crucial roles in lymphopoiesis. In particular, JAK3 has unique functions in the lymphoid system such that JAK3 ablation results in phenotypes resembling severe combined immunodeficiency syndrome. This review focuses on the biochemistry, immunological functions, and clinical significance of JAK3. Compared with other members of the JAK family, the biochemical properties of JAK3 are relatively less well characterized and thus largely inferred from studies of JAK2. Furthermore, new findings concerning the cross-talks between Notch and JAK signaling pathways through ubiquitin-mediated protein degradation are discussed in more detail.

[Abnormality of NF- Kappa B Expression and the Clinical Implications in Patients with HBV-related Hepatocelluar Carcinoma]

Zhonghua Gan Zang Bing Za Zhi = Zhonghua Ganzangbing Zazhi = Chinese Journal of Hepatology. Jun, 2011  |  Pubmed ID: 22053381

Trends in Biomedical Engineering: Focus on Patient Specific Modeling and Life Support Systems

Journal of Applied Biomaterials & Biomechanics : JABB. May-Aug, 2011  |  Pubmed ID: 22065388

Abstract Over the last twenty years major advancements have taken place in the design of medical devices and personalized therapies. They have paralleled the impressive evolution of three-dimensional, non invasive, medical imaging techniques and have been continuously fuelled by increasing computing power and the emergence of novel and sophisticated software tools. This paper aims to showcase a number of major contributions to the advancements of modeling of surgical and interventional procedures and to the design of life support systems. The selected examples will span from pediatric cardiac surgery procedures to valve and ventricle repair techniques, from stent design and endovascular procedures to life support systems and innovative ventilation techniques.

Polymerized Human Placenta Hemoglobin Given Before Ischemia Protects Rat Heart from Ischemia Reperfusion Injury

Artificial Cells, Blood Substitutes, and Immobilization Biotechnology. Dec, 2011  |  Pubmed ID: 22066796

This study was to investigate whether polymerized human placenta hemoglobin (PolyPHb) given before ischemia protects in vivo rat heart function against ischemia/reperfusion (I/R) injury. Forty-five male Sprague-Dawley rats were randomly divided (n = 15 per group) into a sham group, control group (pretreatment with Lactated Ringer's solution), or PolyPHb group (pretreatment with 0.1 gHb/kg PolyPHb). Rat hearts were subjected to 30-min ischemia by occlusion of left anterior descending, followed by 2-hr reperfusion. As compared to the control group, PolyPHb preserved cardiac function and reduced cardiac troponin-I release and histopathological changes. Therefore, PolyPHb pretreatment provided a profound cardioprotective effect on the in vivo rat heart.

[The Analysis on the Allergen Test of the Allergic Rhinitis with 1564 Cases in Changji District]

Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi = Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery. Sep, 2011  |  Pubmed ID: 22070073

To investigate the allergen distribution of subjects suffered from the allergic rhinitis in Changji district.

[Single Nucleotide Polymorphisms of CYP1A2 and Their Correlation with Prostate Cancer]

Zhonghua Nan Ke Xue = National Journal of Andrology. Nov, 2011  |  Pubmed ID: 22141270

To evaluate the correlation of the single nucleotide polymorphisms (SNPs) of the CYP1A2 gene with the stages and grades of prostate cancer (PCa).

[Expression of CK19 MRNA and EGFR MRNA in the Peripheral Blood and Its Relationship with Lymphatic Metastasis in Laryngeal Carcinoma Model]

Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi = Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery. Jun, 2011  |  Pubmed ID: 21845829

To explore clinical evaluate of CK19 mRNA and EGFR mRNA for diagnosis of laryngeal carcinoma micrometastasis, correlation between circulation tumor cell and lymph node metastasis.

Classical Valence Bond Approach by Modern Methods

Chemical Reviews. Nov, 2011  |  Pubmed ID: 21848344

Additional Genomic Duplications in AZFc Underlie the B2/b3 Deletion-associated Risk of Spermatogenic Impairment in Han Chinese Population

Human Molecular Genetics. Nov, 2011  |  Pubmed ID: 21852246

The azoospermia factor c (AZFc) region on the Y chromosome is a genetically dynamic locus in the human genome. Numerous genomic rearrangements, including deletion, duplication and inversion, have been identified in AZFc. The complete deletion of AZFc can cause spermatogenic impairment. However, the roles of partial AZFc deletions (e.g. b2/b3 deletion) in spermatogenesis are controversial and variable among human populations. Secondary duplication has been hypothesized to be a compensatory factor for partial AZFc deletions. To further study genomic duplications in AZFc as a potential genetic modifier underlying the phenotypic variations of partial AZFc deletions in spermatogenesis, we conducted comprehensive molecular analyses in 711 idiopathic infertile men and 390 healthy controls. Unexpectedly, we found that additional AZFc duplications accompanying the b2/b3 deletion, instead of the b2/b3 deletion alone, led to the b2/b3 deletion-associated risk of spermatogenic impairment previously reported in Han Chinese population. In addition, partial AZFc duplication also rendered a risk factor in the non-deletion patients. DAZ is a multi-copy AZFc gene (DAZ1-DAZ4) implicated in spermatogenesis. Genetic variations do exist between DAZ copies. Intriguingly, we found that the DAZ1/2 cluster was the main duplicated copies in the partial AZFc duplications associated with spermatogenic impairment, suggesting a potential different role of spermatogenesis between DAZ copies. Our findings demonstrated that additional AZFc duplications did not compensate but convey the susceptibility of the b2/b3 deletion to spermatogenic impairment in the tested population. Notably, genomic duplications and deletions in AZFc deserve comprehensive investigations to uncover spermatogenic roles of the AZFc region.

Interlevel Cascade Transition in Electrically Confined Quantum Wire Arrays

ACS Nano. Sep, 2011  |  Pubmed ID: 21854062

Vertical stacks of electrically confined quantum wires were demonstrated in devices with large areas. Multiple current plateaus and strong differential conductance oscillations were observed at above liquid nitrogen temperatures because of interlevel cascade transition of carriers. Our simulation results for charge transport, as well as interlevel infrared photoresponse red-shift, due to lateral electric field confinement show good agreement with experimental data.

Clusters of Spatial, Temporal, and Space-time Distribution of Hemorrhagic Fever with Renal Syndrome in Liaoning Province, Northeastern China

BMC Infectious Diseases. 2011  |  Pubmed ID: 21867563

Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease caused by Hantavirus, with characteristics of fever, hemorrhage, kidney damage, and hypotension. HFRS is recognized as a notifiable public health problem in China, and Liaoning Province is one of the most seriously affected areas with the most cases in China. It is necessary to investigate the spatial, temporal, and space-time distribution of confirmed cases of HFRS in Liaoning Province, China for future research into risk factors.

Design of the Image-Guided Biopsy Marking System for Gastroscopy

Journal of Medical Systems. Aug, 2011  |  Pubmed ID: 21870031

Endoscopists currently rely on an invasive biopsy tattooing method to identify previously biopsied sites. In order to better guide endoscopists to find the biopsy positions in follow-ups, we proposed a non-invasive image guided biopsy marking system for gastroscopy. Using an electromagnetic tracking device, the position of the gastroscope relative to the stomach was acquired and displayed in the guidance interface. The biopsy positions were recorded in computer for the use of guidance in follow-ups. The accuracy of the system was evaluated by both phantom experiments and in vivo experiments. The average target registration errors on the test animal and the volunteer are 13.4 mm and 11.2 mm respectively. Although the positioning error is slightly larger than current biopsy tattooing method, it satisfies the need for guidance. In the near future, we will validate the system by measuring how much it saves examination time.

Identification of New Aberrantly Expressed MiRNAs in Intestinal-type Gastric Cancer and Its Clinical Significance

Oncology Reports. Dec, 2011  |  Pubmed ID: 21874264

miRNAs are small 19 to 22 nucleotide sequences of RNA that negatively regulate gene expression. miRNA expression profiles may become useful biomarkers for diagnostics, prognosis and prediction of response to treat, and it could be a powerful tool for cancer prevention and therapeutics. Several miRNA expression profiles of miRNAs in gastric cancer have been reported, but these studies screened only few miRNAs and samples used in experiments include several different subtypes of gastric cancers, which decrease the sensitivity to identify new aberrant miRNAs. In this study, a miRNA expression profile was identified by miRCURY LNA Array (v.14.0) between intestinal-type gastric cancers and normal tissues. Forty miRNA precursors were up-regulated and thirty-six miRNA were down-regulated in intestinal-type gastric cancers (p<0.01). Sixteen new miRNAs were found in intestinal-type gastric cancers. Seventeen new miRNAs were found in intestinal-type gastric cancers. miR-145, miR-27a, miR-494 are differently expressed between intestinal-type and diffuse-type gastric cancers. miR-32, miR-182 and miR-143 dysregulated expression levels are related with different pathological stages of intestinal-type gastric cancers (p<0.01). Taken together, aberrantly expressed miRNAs may offer new clues to tumorigenesis of gastric cancers. miR-32, miR-182 and miR-143 may be potential diagnostic biomarkers for intestinal-type gastric cancers.

Cryopreservation of Tissue-engineered Epithelial Sheets in Trehalose

Biomaterials. Nov, 2011  |  Pubmed ID: 21889199

Tissue-engineered epidermal membranes are useful for clinical wound healing. To facilitate these products in the clinic, optimized storage methods need to be developed. We studied the efficiency of extracellular trehalose at various concentrations for cryopreserving human tissue-engineered epidermal membranes compared with that of dimethyl-sulfoxide (DMSO) used by most organ banks for cryopreserving skin grafts and artificial skin substitutes. Keratinocyte (KC) viability, proliferation and marker expression following cryopreservation in trehalose were examined with similar results to those using DMSO. Trehalose concentration (0.4m) was optimized according to the described cellular activities following cryopreservation. Artificial epidermal substitutes were then cryopreserved in trehalose at the optimized concentration. Cell viability, growth factor secretion and wound healing properties of cryopreserved artificial epidermal substitutes using nude mice were examined and compared with those of DMSO cryopreservation. Cryopreservation with trehalose enhanced human KC viability in suspension and artificial skin substitutes. In addition, trehalose cryopreservation provided fast recovery of EGF and TGF-β1 secretion by KCs after thawing. When transplanted into nude mice, trehalose-cryopreserved artificial skin repaired skin defects in a similar manner to that of a non-cryopreserved control. Moreover, trehalose-cryopreserved artificial skin resulted in engraftment and wound closure that was significantly enhanced compared with that of DMSO-cryopreserved epidermal membranes. The results indicate that the use of trehalose improves cryopreservation of tissue-engineered epithelial sheets.

Prevalence of Dirofilaria Immitis Infection in Dogs from Dandong, China

Veterinary Parasitology. Dec, 2011  |  Pubmed ID: 21889850

The aim of the present study was to estimate the prevalence and risk factors of Dirofilaria immitis infection in dogs from Dandong, China. A total of 886 dogs were examined for D. immitis infection by microscopic examination and PCR, indicating that the prevalence was 16.6% (213/886) and 24.0% (147/886), respectively. The odds of infection were significantly higher in older dogs and dogs sheltered in outdoor, compared to the younger ones and ones sheltered in indoor. No significant difference of infection was observed in different genders, and between pure breed and cross-breed dogs in the same rearing conditions. These results indicated that the risk of exposure to D. immitis in dogs is high in Dandong, China, and prophylaxis against the parasite is advisable to decrease the incidence of canine dirofilariosis.

Association of Atherosclerotic Cerebral Infarction and Human Leukocyte Antigen-DRB in a North Chinese Han Population

Neurology India. Jul-Aug, 2011  |  Pubmed ID: 21891926

Evidence from experimental and genetic studies suggest the existence of a potential link between the polymorphisms of human leukocyte antigen class II gene (HLA-DR) and ischemic stroke. This study addressed the association of HLA-DR gene with atherosclerotic cerebral infarction (ACI) in a North Chinese Han population.

Bivariate and Multivariate NeuroXidence: A Robust and Reliable Method to Detect Modulations of Spike-Spike Synchronization Across Experimental Conditions

Frontiers in Neuroinformatics. 2011  |  Pubmed ID: 21897816

Synchronous neuronal firing has been proposed as a potential neuronal code. To determine whether synchronous firing is really involved in different forms of information processing, one needs to directly compare the amount of synchronous firing due to various factors, such as different experimental or behavioral conditions. In order to address this issue, we present an extended version of the previously published method, NeuroXidence. The improved method incorporates bi- and multivariate testing to determine whether different factors result in synchronous firing occurring above the chance level. We demonstrate through the use of simulated data sets that bi- and multivariate NeuroXidence reliably and robustly detects joint-spike-events across different factors.

Dynamics of Population Response to Changes of Motion Direction in Primary Visual Cortex

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Sep, 2011  |  Pubmed ID: 21900556

The visual system is thought to represent the direction of moving objects in the relative activity of large populations of cortical neurons that are broadly tuned to the direction of stimulus motion, but how changes in the direction of a moving stimulus are represented in the population response remains poorly understood. Here we take advantage of the orderly mapping of direction selectivity in ferret primary visual cortex (V1) to explore how abrupt changes in the direction of a moving stimulus are encoded in population activity using voltage-sensitive dye imaging. For stimuli moving in a constant direction, the peak of the V1 population response accurately represented the direction of stimulus motion, but following abrupt changes in motion direction, the peak transiently departed from the direction of stimulus motion in a fashion that varied with the direction offset angle and was well predicted from the response to the component directions. We conclude that cortical dynamics and population coding mechanisms combine to place constraints on the accuracy with which abrupt changes in direction of motion can be represented by cortical circuits.

The Effect of Hydrophilic Chain Length and IRGD on Drug Delivery from Poly(ε-caprolactone)-poly(N-vinylpyrrolidone) Nanoparticles

Biomaterials. Dec, 2011  |  Pubmed ID: 21903260

Poly(ε-caprolactone)-b-Poly(N-vinylpyrrolidone) (PCL-b-PVP) copolymers with different PVP block length were synthesized by xanthate-mediated reverse addition fragment transfer polymerization (RAFT) and the xanthate chain transfer agent on chain end was readily translated to hydroxy or aldehyde for conjugating various functional moieties, such as fluorescent dye, biotin hydrazine and tumor homing peptide iRGD. Thus, PCL-PVP nanoparticles were prepared by these functionalized PCL-b-PVP copolymers. Furthermore, paclitaxel-loaded PCL-PVP nanoparticles with satisfactory drug loading content (15%) and encapsulation efficiency (>90%) were obtained and used in vitro and in vivo antitumor examination. It was demonstrated that the length of PVP block had a significant influence on cytotoxicity, anti-BSA adsorption, circulation time, stealth behavior, biodistribution and antitumor activity for the nanoparticles. iRGD on PCL-PVP nanoparticle surface facilitated the nanoparticles to accumulate in tumor site and enhanced their penetration in tumor tissues, both of which improved the efficacy of paclitaxel-loaded nanoparticles in impeding tumor growth and prolonging the life time of H22 tumor-bearing mice.

Acacetin Causes a Frequency- and Use-dependent Blockade of HKv1.5 Channels by Binding to the S6 Domain

Journal of Molecular and Cellular Cardiology. Dec, 2011  |  Pubmed ID: 21906601

We have demonstrated that the natural flavone acacetin selectively inhibits ultra-rapid delayed rectifier potassium current (I(Kur)) in human atria. However, molecular determinants of this ion channel blocker are unknown. The present study was designed to investigate the molecular determinants underlying the ability of acacetin to block hKv1.5 channels (coding I(Kur)) in human atrial myocytes using the whole-cell patch voltage-clamp technique to record membrane current in HEK 293 cells stably expressing the hKv1.5 gene or transiently expressing mutant hKv1.5 genes generated by site-directed mutagenesis. It was found that acacetin blocked hKv1.5 channels by binding to both closed and open channels. The blockade of hKv1.5 channels by acacetin was use- and frequency-dependent, and the IC(50) of acacetin for inhibiting hKv1.5 was 3.5, 3.1, 2.9, 2.1, and 1.7μM, respectively, at 0.2, 0.5, 1, 3, and 4Hz. The mutagenesis study showed that the hKv1.5 mutants V505A, I508A, and V512A in the S6-segment remarkably reduced the channel blocking properties by acacetin (IC(50), 29.5μM for V505A, 19.1μM for I508A, and 6.9μM for V512A). These results demonstrate the novel information that acacetin mainly blocks open hKv1.5 channels by binding to their S6 domain. The use- and rate-dependent blocking of hKv1.5 by acacetin is beneficial for anti-atrial fibrillation.

NIR-light-induced Deformation of Cross-linked Liquid-crystal Polymers Using Upconversion Nanophosphors

Journal of the American Chemical Society. Oct, 2011  |  Pubmed ID: 21913658

When upconversion nanophosphors were incorporated into an azotolane-containing cross-linked liquid-crystal polymer film, the resulting composite film generated fast bending upon exposure to continuous-wave near-IR light at 980 nm. This occurs because the upconversion luminescence of the nanophosphors leads to trans-cis photoisomerization of the azotolane units and an alignment change of the mesogens. The bent film completely reverted to the initial flat state after the light source was removed.

Integrative Analysis of Transcriptome and Genome Indicates Two Potential Genomic Islands Are Associated with Pathogenesis of Mycobacterium Tuberculosis

Gene. Dec, 2011  |  Pubmed ID: 21924330

Mycobacterium tuberculosis (M.tb) is a successful human pathogen and widely prevalent throughout the world. Genomic islands (GIs) are thought to be related to pathogenicity. In this study, we predicted two potential genomic islands in M.tb genome, respectively named as GI-1 and GI-2. It is indicated that the genes belong to PE_PGRS family in GI-1 and genes involved in sulfolipid-1 (SL-1) synthesis in GI-2 are strongly associated with M.tb pathogenesis. Sequence analysis revealed that the five PGRS genes are more polymorphic than other PGRS members in full virulence M.tb complex strains at significance level 0.01 but not in attenuated strains. Expression analysis of microarrays collected from literatures displayed that GI-1 genes, especially Rv3508 might be correlated with the response to the inhibition of aerobic respiration. Microarray analysis also showed that SL-1 cluster genes are drastically down-expressed in attenuated strains relative to full virulence strains. We speculated that the effect of SL-1 on M.tb pathogenicity could be associated with long-term survival and persistence establishment during infection. Additionally, the gene Rv3508 in GI-1 was under positive selection. Rv3508 may involve the response of M.tb to the inhibition of aerobic respiration by low oxygen or drug PA-824, and it may be a common feature of genes in GI-1. These findings may provide some novel insights into M.tb physiology and pathogenesis.

Assemblathon 1: a Competitive Assessment of De Novo Short Read Assembly Methods

Genome Research. Dec, 2011  |  Pubmed ID: 21926179

Low-cost short read sequencing technology has revolutionized genomics, though it is only just becoming practical for the high-quality de novo assembly of a novel large genome. We describe the Assemblathon 1 competition, which aimed to comprehensively assess the state of the art in de novo assembly methods when applied to current sequencing technologies. In a collaborative effort, teams were asked to assemble a simulated Illumina HiSeq data set of an unknown, simulated diploid genome. A total of 41 assemblies from 17 different groups were received. Novel haplotype aware assessments of coverage, contiguity, structure, base calling, and copy number were made. We establish that within this benchmark: (1) It is possible to assemble the genome to a high level of coverage and accuracy, and that (2) large differences exist between the assemblies, suggesting room for further improvements in current methods. The simulated benchmark, including the correct answer, the assemblies, and the code that was used to evaluate the assemblies is now public and freely available from http://www.assemblathon.org/.

Nonlinear Responses in Optical Metamaterials: Theory and Experiment

Optics Express. Sep, 2011  |  Pubmed ID: 21935195

We employed both theoretical calculations and experiments to study the nonlinear responses in optical metamaterials. The spectra of second-harmonic generations measured on a fishnet metamaterial are in quantitative agreements with calculations based on full-wave numerical simulations combined with field integrations, both exhibiting ~80 times enhancements at the magnetic resonance frequency. Our calculations explained several interesting features observed experimentally, and suggested an optimal metamaterial structure to yield the strongest nonlinear signals.

Controlled Synthesis of Magnetic Iron Oxides@SnO2 Quasi-hollow Core-shell Heterostructures: Formation Mechanism, and Enhanced Photocatalytic Activity

Nanoscale. Nov, 2011  |  Pubmed ID: 21947413

Iron oxide/SnO(2) magnetic semiconductor core-shell heterostructures with high purity were synthesized by a low-cost, surfactant-free and environmentally friendly hydrothermal strategy via a seed-mediated method. The morphology and structure of the hybrid nanostructures were characterized by means of high-resolution transmission electron microscopy and X-ray diffraction. The morphology evolution investigations reveal that the Kirkendall effect directs the diffusion and causes the formation of iron oxide/SnO(2) quasi-hollow particles. Significantly, the as-obtained iron oxides/SnO(2) core-shell heterostructures exhibited enhanced visible light or UV photocatalytic abilities, remarkably superior to as-used α-Fe(2)O(3) seeds and commercial SnO(2) products, mainly owing to the effective electron hole separation at the iron oxides/SnO(2) interfaces.

Silymarin Glyceryl Monooleate/poloxamer 407 Liquid Crystalline Matrices: Physical Characterization and Enhanced Oral Bioavailability

AAPS PharmSciTech. Dec, 2011  |  Pubmed ID: 21948306

Silymarin, a mixture of flavonolignans extracted from the seeds of milk thistle, is used clinically as a hepatoprotector to treat liver injuries and chronic hepatitis. However, its therapeutic effect is compromised by its poor oral bioavailability due to the poor solubility and low permeability across intestinal epithelia. The main purpose of this study was to prepare silymarin glyceryl monooleate/poloxamer 407 liquid crystalline matrices (GMO/P407 LCM) to improve the oral bioavailability of silymarin. GMO/P407 LCMs were prepared by a melting/congealing method. The isotropic phenomenon observed under polarized light microscope confirmed the liquid crystalline structure at the junction of LCM and water. Both differential scanning calorimetry and X-ray diffraction analysis confirmed disappearance of silymarin crystallinity after incorporation into the LCMs. In vitro release of silymarin from LCMs was limited, whereas LCMs were readily degraded by lipase and released silymarin quickly and completely. Pharmacokinetic study in beagle dogs showed significantly increased peak concentration for silymarin GMO/P407 LCM, and, most importantly, a 3.46-fold increase in oral bioavailability as compared with Legalon®, a commercial silymarin formulation.

Growth of Single Crystal Graphene Arrays by Locally Controlling Nucleation on Polycrystalline Cu Using Chemical Vapor Deposition

Advanced Materials (Deerfield Beach, Fla.). Nov, 2011  |  Pubmed ID: 21953626

[Y-chromosome Microdeletions Do Not Affect the Outcomes of ICSI for Infertile Males]

Zhonghua Nan Ke Xue = National Journal of Andrology. Sep, 2011  |  Pubmed ID: 21961234

To compare the outcomes of intracytoplasmic sperm injection (ICSI) for infertile males with Y-chromosome microdeletions and for those with azoospermia or severe oligospermia but without Y-chromosome microdeletions.

Facile Method to Synthesize Magnetic Iron Oxides/TiO2 Hybrid Nanoparticles and Their Photodegradation Application of Methylene Blue

Nanoscale Research Letters. 2011  |  Pubmed ID: 21961891

ABSTRACT: Many methods have been reported to improving the photocatalytic efficiency of organic pollutant and their reliable applications. In this work, we propose a facile pathway to prepare three different types of magnetic iron oxides/TiO2 hybrid nanoparticles (NPs) by seed-mediated method. The hybrid NPs are composed of spindle, hollow, and ultrafine iron oxide NPs as seeds and 3-aminopropyltriethyloxysilane as linker between the magnetic cores and TiO2 layers, respectively. The composite structure and the presence of the iron oxide and titania phase have been confirmed by transmission electron microscopy, X-ray diffraction, and X-ray photoelectron spectra. The hybrid NPs show good magnetic response, which can get together under an external applied magnetic field and hence they should become promising magnetic recovery catalysts (MRCs). Photocatalytic ability examination of the magnetic hybrid NPs was carried out in methylene blue (MB) solutions illuminated under Hg light in a photochemical reactor. About 50% to 60% of MB was decomposed in 90 min in the presence of magnetic hybrid NPs. The synthesized magnetic hybrid NPs display high photocatalytic efficiency and will find recoverable potential applications in cleaning polluted water with the help of magnetic separation.

Necroptosis: An Emerging Form of Programmed Cell Death

Critical Reviews in Oncology/hematology. Sep, 2011  |  Pubmed ID: 21962882

Necrosis plays an important role in multiple physiological and pathological processes. Recently, a relatively new form of necrosis has been characterized as "necroptosis". Morphologically, necroptosis exhibits the features of necrosis; however, necroptosis exhibits a unique signaling pathway that requires the involvement of receptor interaction protein kinase 1 and 3 (RIP1 and RIP3) and can be specifically inhibited by necrostatins. Necroptosis has been found to contribute to the regulation of immune system, cancer development as well as cellular responses to multiple stresses. In this review, we will summarize the signaling pathway, biological effects and pathological significance of this specific form of programmed cell death.

A Mechanism Underlying NOTCH-induced and Ubiquitin-mediated JAK3 Degradation

The Journal of Biological Chemistry. Dec, 2011  |  Pubmed ID: 21969365

Although NOTCH signaling is well known to regulate lymphopoiesis, Janus kinase 3 (JAK3) also plays a critical role in promoting lymphocyte development. We have previously found that NOTCH signaling leads to the degradation of JAK3 in B lineage cells, suggesting that NOTCH signaling exerts its biological effect on lymphopoiesis through modulating JAK3 levels. Here, we delineate the biochemical mechanisms involved in NOTCH-induced JAK3 ubiquitination and degradation. NOTCH signaling is known to transcriptionally activate the genes encoding ASB2 (ankyrin-repeat SOCS box containing protein 2) and SKP2 (S-phase kinase-associated protein 2). We show that not only NOTCH but also ASB2 and SKP2 can promote the ubiquitination and degradation of JAK3. Both ASB2 and SKP2 can interact with JAK3 through different domains; the FERM and pseudo-kinase domains each had high affinities for ASB2, whereas the kinase domain primarily associated with SKP2. ASB2 and SKP2 previously have been shown to associate with each other to bridge the formation of a non-canonical Cullin1 and Cullin5-containing dimeric E3 ligase complex. Interestingly, the R980W mutant of JAK3 exhibited diminished interaction with SKP2 and resistance to NOTCH or ASB2-induced degradation. Furthermore, dominant-negative mutants of either Cullin1 or Cullin5, which lack the C terminus responsible for recruiting the E2 enzymes, were able to prevent JAK3 degradation induced by both ASB2/SKP2 and NOTCH signaling. Together, these results suggest that JAK3 ubiquitination involves the non-canonical dimeric E3 ligase complex, and the R980W mutant will serve as an excellent tool for investigating the biological significance of NOTCH-mediated JAK3 turnover.

Using SAS PROC TCALIS for Multigroup Structural Equation Modelling with Mean Structures

The British Journal of Mathematical and Statistical Psychology. Nov, 2011  |  Pubmed ID: 21973099

Multigroup structural equation modelling (SEM) is a technique frequently used to evaluate measurement invariance in social and behavioural science research. Before version 9.2, SAS was incapable of handling multigroup SEM. However, this limitation is resolved in PROC TCALIS in SAS 9.2. For the purpose of illustration, this paper provides a step-by-step guide to programming the tests of measurement invariance and partial invariance using PROC TCALIS for multigroup SEM with mean structures. Fit indices and parameter estimates are validated, thus providing an alternative tool for researchers conducting both applied and simulated studies. Other new features (e.g., different types of modelling languages and estimation methods) and limitations (e.g., ordered-categorical SEM and multilevel SEM) of the TCALIS procedure are also briefly discussed.

Characterization of Glycosylation Sites for a Recombinant IgG1 Monoclonal Antibody and a CTLA4-Ig Fusion Protein by Liquid Chromatography-mass Spectrometry Peptide Mapping

Journal of Chromatography. A. Nov, 2011  |  Pubmed ID: 21978954

Liquid chromatography mass spectrometry (LC-MS) peptide mapping can be a versatile technique for characterizing protein glycosylation sites without the need to remove the attached glycans as in conventional oligosaccharide mapping methods. In this way, both N-linked and O-linked sites of glycosylation can each be directly identified, characterized, and quantified by LC-MS as intact glycopeptides in a single experiment. LC-MS peptide mapping of the individual glycosylation sites avoids many of the limitations of preparing and analyzing an entire pool of released N-linked oligosaccharides from all sites mixed together. In this study, LC interfaced to a linear ion trap mass spectrometer (ESI-LIT-MS) were used to characterize the glycosylation of a recombinant IgG1 monoclonal antibody and a CTLA4-Ig fusion protein with multiple sites of N-and O-glycosylation. Samples were reduced, S-carboxyamidomethylated, and cleaved with either trypsin or endoproteinase Asp-N. Enhanced detection for minor IgG1 glycoforms (∼0.1 to 1.0 mol% level) was obtained by LC-MS of the longer 32-residue Asp-N glycopeptide (4+ protonated ion) compared to the 9-residue tryptic glycopeptide (2+ ion). LC-MS peptide mapping was run according to a general procedure: (1) Locate N-linked and/or O-linked sites of glycosylation by selected-ion-monitoring of carbohydrate oxonium fragment ions generated by ESI in-source collision-induced dissociation (CID), i.e. 204, 366, and 292 Da marker ions for HexNAc, HexNAc-Hex, and NeuAc, respectively; (2) Characterize oligosaccharides at each site via MS and MSMS. Use selected ion currents (SIC) to estimate relative amounts of each glycoform; and (3) Measure the percentage of site-occupancy by searching for any corresponding nonglycosylated peptide.

New Insight into Praziquantel Against Various Developmental Stages of Schistosomes

Parasitology Research. Dec, 2011  |  Pubmed ID: 21984370

Praziquantel, due to high efficacy, excellent tolerability, few and transient side effects, simple administration, and competitive cost, is virtually the only drug of choice for treatment of human schistosomiasis. Treatment of schistosomiasis has shown great advances with the introduction of the drug into the therapeutic arsenal in areas that are endemic for the parasite. However, the drug presents various efficacies against different developmental stages of schistosomes, appearing an oddity intermitted mode. The present review article reviews the effects and mechanism of action of praziquantel against schistosomes briefly and suggests the research on this oddity phenomenon.

High Prevalence of Coexisting Prehypertension and Prediabetes Among Healthy Adults in Northern and Northeastern China

BMC Public Health. 2011  |  Pubmed ID: 21988955

Prehypertension and prediabetes are major risk factors of cardiovascular disease, and their combined presence may result in more serious cardiovascular outcomes than expected with either prehypertension or prediabetes alone. The aim of the present study was to evaluate the prevalence of coexisting prehypertension and prediabetes, and the associated risk profiles in a Chinese population.

Inhibition of Voltage-gated Sodium Channels by Emulsified Isoflurane May Contribute to Its Subarachnoid Anesthetic Effect in Beagle Dogs

Regional Anesthesia and Pain Medicine. Nov-Dec, 2011  |  Pubmed ID: 21989153

Volatile anesthetics, in addition to their general anesthesia action, have been proven to produce regional anesthetic effect in various animal models. The major aim of this study was to examine whether emulsified isoflurane (EI) could also produce subarachnoid anesthesia and to investigate its possible mechanism.

STAT3 Knockdown Reduces Pancreatic Cancer Cell Invasiveness and Matrix Metalloproteinase-7 Expression in Nude Mice

PloS One. 2011  |  Pubmed ID: 21991388

Transducer and activator of transcription-3 (STAT3) plays an important role in tumor cell invasion and metastasis. The aim of the present study was to investigate the effects of STAT3 knockdown in nude mouse xenografts of pancreatic cancer cells and underlying gene expression.

Inhibitory Effect of Blueberry Polyphenolic Compounds on Oleic Acid-induced Hepatic Steatosis in Vitro

Journal of Agricultural and Food Chemistry. Nov, 2011  |  Pubmed ID: 21999238

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide and is closely associated with metabolic syndromes, such as obesity, diabetes, and insulin resistance. Nonalcoholic fatty liver (NAFL), also called simple steatosis, is the initial phase of NAFLD, which is accompanied the characteristic pathological overaccumulation of lipids without inflammation. To prevent NAFLD from reaching the NAFL stage through dietary therapy, in the present work, wild Chinese blueberries (Vacciniun spp.) were selected for their well-known benefits in inhibiting metabolic syndrome. After being purified from wild Chinese blueberries, polyphenol-rich extracts were subsequently separated into three fractions, namely, anthocyanin-rich fraction, phenolic acid-rich fraction, and ethyl acetate extract. The inhibition of oleic acid (OA)-induced triglyceride (TG) deposition in HepG 2 cells was referred to as the potential activity of preventing NAFL. Biochemical indicators, such as cytotoxicity, TG level, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and intracellular reactive oxygen species, were used to evaluate the analogous pathological stage of NAFLD. The results show that OA ≤ 1.0 mM exhibits a dose-dependent induction of TG accumulation, and no inflammation was observed based on the changes in ALT and AST levels. Therefore, 1.0 mM OA was used to simulate an in vitro fatty liver. Blueberry polyphenol-rich extract efficiently inhibited OA-induced TG accumulation in HepG2 cells, and the phenolic acid-rich fraction performed efficiently. Seven phenolic acids were subsequently identified using a high-performance liquid chromatography assay, and the main types were caffeic, chlorogenic, ferulic, p-coumaric, and cinnamic acids. These phenolic acid standards also displayed good efficiency in inhibiting TG accumulation in HepG2 cells. These results imply that wild Chinese blueberries have a potential preventive effect on NAFLD in its early stage, and phenolic acids are the most efficient component.

[Mannose-binding Lectin (MBL) Inhibits Human Cytomegalovirus Infection of Human MD-DC]

Sichuan Da Xue Xue Bao. Yi Xue Ban = Journal of Sichuan University. Medical Science Edition. Sep, 2011  |  Pubmed ID: 22007480

To explore the inhibitory effect of different sources, different concentrations of Mannose-binding lectin (MBL) on human cytomegalovirus infection of human MD-DC cells.

The Study on Causes of Death in Fulminant Pancreatitis at Early Stage and Late Stage

Sichuan Da Xue Xue Bao. Yi Xue Ban = Journal of Sichuan University. Medical Science Edition. Sep, 2011  |  Pubmed ID: 22007499

To investigate clinical characteristics of fulminant pancreatitis (FP) died at early and late stage, analyze the difference in death causes of FP at these two stage.

[Protective Effect of Hydroxysafflor Yellow A on Endothelial Cell Injury Induced by Lipopolysaccharide]

Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica. Jun, 2011  |  Pubmed ID: 22007554

To observe the protective effect of hydroxyl safflor yellow A (HSYA) on endothelial cell (EC). It has been observed by RT-PCR that HSYA can inhibit the elevation of TNF-alpha, IL-6, ICAM-1 and VCAM-1 mRNA level induced by LPS. The result of immunofluorescence test suggested that HSYA can alleviate p65 subgroup of NF-kappaB nuclear translocation. The experiment on EA-HY926 cell line proved that HSYA can protect EC against inflammation injury.

Spike Rate and Spike Timing Contributions to Coding Taste Quality Information in Rat Periphery

Frontiers in Integrative Neuroscience. 2011  |  Pubmed ID: 21617730

There is emerging evidence that individual sensory neurons in the rodent brain rely on temporal features of the discharge pattern to code differences in taste quality information. In contrast, investigations of individual sensory neurons in the periphery have focused on analysis of spike rate and mostly disregarded spike timing as a taste quality coding mechanism. The purpose of this work was to determine the contribution of spike timing to taste quality coding by rat geniculate ganglion neurons using computational methods that have been applied successfully in other systems. We recorded the discharge patterns of narrowly tuned and broadly tuned neurons in the rat geniculate ganglion to representatives of the five basic taste qualities. We used mutual information to determine significant responses and the van Rossum metric to characterize their temporal features. While our findings show that spike timing contributes a significant part of the message, spike rate contributes the largest portion of the message relayed by afferent neurons from rat fungiform taste buds to the brain. Thus, spike rate and spike timing together are more effective than spike rate alone in coding stimulus quality information to a single basic taste in the periphery for both narrowly tuned specialist and broadly tuned generalist neurons.

MDM2 SNP309, Gene-gene Interaction, and Tumor Susceptibility: an Updated Meta-analysis

BMC Cancer. 2011  |  Pubmed ID: 21619694

The tumor suppressor gene p53 is involved in multiple cellular pathways including apoptosis, transcriptional control, and cell cycle regulation. In the last decade it has been demonstrated that the single nucleotide polymorphism (SNP) at codon 72 of the p53 gene is associated with the risk for development of various neoplasms. MDM2 SNP309 is a single nucleotide T to G polymorphism located in the MDM2 gene promoter. From the time that this well-characterized functional polymorphism was identified, a variety of case-control studies have been published that investigate the possible association between MDM2 SNP309 and cancer risk. However, the results of the published studies, as well as the subsequent meta-analyses, remain contradictory.

[Detecting DNA Damage of Human Lymphocytes Exposed to 1,2-DCE with γH2AX Identified Antibody Using Flow Cytometer Assay]

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi = Zhonghua Laodong Weisheng Zhiyebing Zazhi = Chinese Journal of Industrial Hygiene and Occupational Diseases. Jan, 2011  |  Pubmed ID: 21619789

To study DNA damage of human peripheral blood lymphocytes exposed to 1,2-dichloroethane (1,2-DCE) with flow cytometry (FCM) assay.

Effects of Ion Channels on Proliferation in Cultured Human Cardiac Fibroblasts

Journal of Molecular and Cellular Cardiology. Aug, 2011  |  Pubmed ID: 21620856

Our previous study demonstrated that multiple ion channels were heterogeneously expressed in human cardiac fibroblasts, including a large-conductance Ca(2+)-activated K(+) current (BKCa), a volume-sensitive chloride current (I(Cl.vol)), and voltage-gated sodium currents (I(Na)). The present study was designed to examine the possible involvement of these ion channels in proliferation of cultured human cardiac fibroblasts using approaches of cell proliferation assay, whole-cell patch voltage-clamp, siRNA and Western blot analysis. It was found that the blockade of BKCa with paxilline (1-3μM) or I(Cl.vol) with 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid disodium (DIDS, 100-200μM), but not I(Na) with tetrodotoxin (0.1-10μM), remarkably suppressed proliferation in human cardiac fibroblasts. Knockdown of KCa1.1 or Clcn3 with specific siRNAs significantly reduced BKCa or I(Cl.vol) current, mRNA and channel protein levels, and inhibited growth of human cardiac fibroblasts. Flow cytometry analysis showed accumulation of cardiac fibroblasts at G0/G1 phase and reduced cell number in S phase after inhibition of BKCa or I(Cl.vol) with channel blockers or knock down of the corresponding channels with specific siRNAs; these effects were accompanied by a decreased expression of cyclin D1 and cyclin E. The present results demonstrate the novel information that BKCa and I(Cl.vol) channels, but not I(Na) channels, are involved in the regulation of proliferation in cultured human cardiac fibroblasts by promoting cell cycle progression via modulating cyclin D1 and cyclin E expression.

Streamlined Protein Expression and Purification Using Cleavable Self-aggregating Tags

Microbial Cell Factories. 2011  |  Pubmed ID: 21631955

Recombinant protein expression and purification remains a fundamental issue for biotechnology. Recently we found that two short self-assembling amphipathic peptides 18A (EWLKAFYEKVLEKLKELF) and ELK16 (LELELKLKLELELKLK) can induce the formation of active protein aggregates in Escherichia coli (E. coli), in which the target proteins retain high enzymatic activities. Here we further explore this finding to develop a novel, facile, matrix-free protein expression and purification approach.

[Enhanced Bioremediation of Coking Plant Soils Contaminated with Polycyclic Aromatic Hydrocarbons]

Huan Jing Ke Xue= Huanjing Kexue / [bian Ji, Zhongguo Ke Xue Yuan Huan Jing Ke Xue Wei Yuan Hui "Huan Jing Ke Xue" Bian Ji Wei Yuan Hui.]. Mar, 2011  |  Pubmed ID: 21634189

Soil samples contaminated with polycyclic aromatic hydrocarbons (PAHs) were collected from Beijing Coking Plant. The purposes were to isolate PAHs degrading bacteria from the soils, determine their appropriate living condition, enrich them and apply them in the enhanced bioremediation of the contaminated soils. Using each of the 16 USEPA priority PAHs as the sole carbon source, PAHs degrading bacteria were isolated using the method of plate streaking and identified by genetic analysis. In total seven species of PAHs degrading bacteria were obtained. When mixed, these bacteria could degrade the 16 (2-6 cyclic) PAHs studied at appropriate concentrations. In the liquid medium, when the total concentration of the 16 PAHs (sigma PAH16) was 17 microg/mL, single bacteria could grow well and degrade the PAHs. However, when sigma PAH16 was 166 microg/mL, the growth and activity of either single PAHs degrading bacteria or a mixture of the seven PAHs degrading bacteria were inhibited. Aiming at the contaminated soils from Beijing coking plant, five treatments were performed, i.e., control (C), addition of nutrient (N), addition of nutrient and PAHs degrading bacteria (N + B), addition of nutrient and surfactant (N +S), addition of nutrient and PAHs degrading bacteria and surfactant (N + B + S). After five weeks of experiment, compared to the C treatment, the mean removal rate of the 16 PAHs in the N + B treatment was increased 32%, and the mean removal rate of the 16 PAHs in the N + B + S treatment was increased 46% (the mean removal rate of the 10 4-6 cyclic PAHs was increased 52%). The addition of PAHs degrading bacteria and surfactant could significantly enhance the degradation of PAHs in the soils. This study provides evidence for the enhanced bioremediation of PAHs contaminated soil for Beijing coking plant and other coking plants.

MicroRNA-21 Targets Peroxisome Proliferators-activated Receptor-alpha in an Autoregulatory Loop to Modulate Flow-induced Endothelial Inflammation

Proceedings of the National Academy of Sciences of the United States of America. Jun, 2011  |  Pubmed ID: 21636785

Adhesion of circulating monocytes to vascular endothelial cells (ECs) is a critical event leading to vascular inflammation and, hence, development of atherosclerosis. MicroRNAs (miRs) are a class of endogenous, highly conserved, noncoding small RNAs that play important roles in regulating gene expression and cellular function, as well as pathogenesis of atherosclerosis. Here, we showed that oscillatory shear stress (OSS) induces the expression of miR-21 at the transcriptional level in cultured human umbilical vein ECs via an increased binding of c-Jun, which is a component of transcription factor activator protein-1 (AP-1), to the promoter region of miR-21. OSS induction of miR-21 inhibited the translation, but not transcription, of peroxisome proliferators-activated receptor-α (PPARα) by 3'-UTR targeting. Overexpression of miR-21 up-regulated AP-1 activation, which was attenuated by exogenous expression of PPARα. OSS and overexpression of miR-21 enhanced the expression of adhesion molecules vascular cell adhesion molecule-1 and monocyte chemotactic protein-1 and the consequential adhesion of monocytes to ECs. Overexpression of PPARα significantly attenuated the AP-1-mediated miR-21 expression. These results demonstrate a unique mechanism by which OSS induces AP-1-dependent miR-21 expression, which directly targets PPARα to inhibit its expression, thereby allowing activation of AP-1 and the promotion of monocyte adhesion. Our findings suggest the presence of a positive feedback loop that enables the sustained induction of miR-21, thus contributing to the proinflammatory responses of vascular endothelium under OSS.

Effect of Alpha-glucosidase Inhibitors on the Progression of Carotid Intima-media Thickness: a Meta-analysis of Randomized Controlled Trials

Atherosclerosis. Sep, 2011  |  Pubmed ID: 21640349

It remains unclear whether lowering postprandial glucose by alpha-glucosidase inhibitors (alpha-GIs) can prevent the progression of carotid intima-media thickness (IMT).

Deletion of Multispecific Organic Anion Transporter Oat1/Slc22a6 Protects Against Mercury-induced Kidney Injury

The Journal of Biological Chemistry. Jul, 2011  |  Pubmed ID: 21652719

The primary site of mercury-induced injury is the kidney due to uptake of the reactive Hg(2+)-conjugated organic anions in the proximal tubule. Here, we investigated the in vivo role of Oat1 (organic anion transporter 1; originally NKT (Lopez-Nieto, C. E., You, G., Bush, K. T., Barros, E. J., Beier, D. R., and Nigam, S. K. (1997) J. Biol. Chem. 272, 6471-6478)) in handling of known nephrotoxic doses of HgCl(2). Oat1 (Slc22a6) is a multispecific organic anion drug transporter that is expressed on the basolateral aspects of renal proximal tubule cells and that mediates the initial steps of elimination of a broad range of endogenous metabolites and commonly prescribed pharmaceuticals. Mercury-induced nephrotoxicity was observed in a wild-type model. We then used the Oat1 knock-out to determine in vivo whether the renal injury effects of mercury are mediated by Oat1. Most of the renal injury (both histologically and biochemically as measured by blood urea nitrogen and creatinine) was abolished following HgCl(2) treatment of Oat1 knock-outs. Thus, acute kidney injury by HgCl(2) was found to be mediated mainly by Oat1. Our findings raise the possibility that pharmacological modulation of the expression and/or function of Oat1 might be an effective therapeutic strategy for reducing renal injury by mercury. This is one of the most striking phenotypes so far identified in the Oat1 knock-out. (Eraly, S. A., Vallon, V., Vaughn, D. A., Gangoiti, J. A., Richter, K., Nagle, M., Monte, J. C., Rieg, T., Truong, D. M., Long, J. M., Barshop, B. A., Kaler, G., and Nigam, S. K. (2006) J. Biol. Chem. 281, 5072-5083).

Oncofetal Antigen Glypican-3 As a Promising Early Diagnostic Marker for Hepatocellular Carcinoma

Hepatobiliary & Pancreatic Diseases International : HBPD INT. Jun, 2011  |  Pubmed ID: 21669573

Hepatocellular carcinoma (HCC) is characterized by a multi-cause, multi-stage and multi-focus process of tumor progression. Its prognosis is poor and early diagnosis is of utmost importance. This study was undertaken to investigate the dynamic expression of oncofetal antigen glypican-3 (GPC-3) and GPC-3 mRNA in hepatocarcinogenesis and to explore their early diagnostic value for HCC.

Calculation of the Modulation Transfer Function for Object Brightness Distribution Function Oriented Along Any Direction in Axis-symmetrical Optical Systems

Applied Optics. Jun, 2011  |  Pubmed ID: 21673782

The literature deals with the modulation transfer function (MTF) only for object brightness distribution functions (OBDFs) oriented along the meridional and sagittal directions. This paper addresses computation of the geometrical MTF for an off-axis source point when the OBDF is oriented along any arbitrarily defined direction. This study finds that the MTF is not a monotonic increasing or decreasing function when the direction of the OBDF is changing. Consequently, the extreme MTF values may occur when the OBDF is aligned at any direction between the meridional and sagittal directions. Four theorems are provided for the MTF and the phase shift variations that take place when the OBDF is translated or rotated. It is found that the MTF and the phase shift are symmetrical or antisymmetrical about certain directions. Thus, to observe all possible changes in the MTF and the phase shift, it is sufficient to rotate the OBDF through a range of just 90°. The presented method is based on a recent irradiance method for MTF computation that does not rely on counting the number of ray hits on a mesh, making the method immune to effects of grid size and thus improving traditional accuracy.

A Practical Strategy for Constructing Nanodrugs Using Carbon Nanotubes As Carriers

Methods in Molecular Biology (Clifton, N.J.). 2011  |  Pubmed ID: 21674355

Carbon nanotubes, acting as nanocarriers, can be combined with drug molecules through various chemical or physical routes in which hydrophilic modifications of the nanotubes are required. Such types of hydrophilic modifications typically involve addition reactions at the nanotube sidewalls, the reactions of nanotube-bound carboxylic groups, and/or coating of the nanotubes with amphiphilic molecules. In this chapter, we introduce detailed approaches for covalently linking drug compounds to multiwalled carbon nanotubes, as well as labeling the synthesized drug-bearing carbon nanotube conjugates with fluorescent or radioactive molecules.

Minimal Regulatory Spaces in Yeast Genomes

BMC Genomics. 2011  |  Pubmed ID: 21679449

The regulatory information encoded in the DNA of promoter regions usually enforces a minimal, non-zero distance between the coding regions of neighboring genes. However, the size of this minimal regulatory space is not generally known. In particular, it is unclear if minimal promoter size differs between species and between uni- and bi-directionally acting regulatory regions.

Spontaneous Aneurysm of the Superficial Temporal Artery

Lancet. Jul, 2011  |  Pubmed ID: 21683996

TREEGL: Reverse Engineering Tree-evolving Gene Networks Underlying Developing Biological Lineages

Bioinformatics (Oxford, England). Jul, 2011  |  Pubmed ID: 21685070

Estimating gene regulatory networks over biological lineages is central to a deeper understanding of how cells evolve during development and differentiation. However, one challenge in estimating such evolving networks is that their host cells not only contiguously evolve, but also branch over time. For example, a stem cell evolves into two more specialized daughter cells at each division, forming a tree of networks. Another example is in a laboratory setting: a biologist may apply several different drugs individually to malignant cancer cells to analyze the effects of each drug on the cells; the cells treated by one drug may not be intrinsically similar to those treated by another, but rather to the malignant cancer cells they were derived from.

Real-time CARS Imaging Reveals a Calpain-dependent Pathway for Paranodal Myelin Retraction During High-frequency Stimulation

PloS One. 2011  |  Pubmed ID: 21390223

High-frequency electrical stimulation is becoming a promising therapy for neurological disorders, however the response of the central nervous system to stimulation remains poorly understood. The current work investigates the response of myelin to electrical stimulation by laser-scanning coherent anti-Stokes Raman scattering (CARS) imaging of myelin in live spinal tissues in real time. Paranodal myelin retraction at the nodes of Ranvier was observed during 200 Hz electrical stimulation. Retraction was seen to begin minutes after the onset of stimulation and continue for up to 10 min after stimulation was ceased, but was found to reverse after a 2 h recovery period. The myelin retraction resulted in exposure of Kv 1.2 potassium channels visualized by immunofluorescence. Accordingly, treating the stimulated tissue with a potassium channel blocker, 4-aminopyridine, led to the appearance of a shoulder peak in the compound action potential curve. Label-free CARS imaging of myelin coupled with multiphoton fluorescence imaging of immuno-labeled proteins at the nodes of Ranvier revealed that high-frequency stimulation induced paranodal myelin retraction via pathologic calcium influx into axons, calpain activation, and cytoskeleton degradation through spectrin break-down.

Tim-3 Expression on Peripheral T Cell Subsets Correlates with Disease Progression in Hepatitis B Infection

Virology Journal. 2011  |  Pubmed ID: 21392402

T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3) represents a novel mechanism of T-cell dysfunction in chronic viral diseases. However, the role of Tim-3 in the pathogenesis of chronic hepatitis B (CHB) is not well understood. We investigated Tim-3 expression on peripheral T cell subsets and analyzed the relationship between Tim-3 expression and disease progression in HBV infection.

Drug Release Behaviors of a PH Sensitive Semi-interpenetrating Polymer Network Hydrogel Composed of Poly(vinyl Alcohol) and Star Poly[2-(dimethylamino)ethyl Methacrylate]

International Journal of Pharmaceutics. Sep, 2011  |  Pubmed ID: 21704139

A series of pH sensitive semi-interpenetrating polymer network (semi-IPN) structural hydrogels composed of poly(vinyl alcohol) (PVA) and 21-arm star poly[2-(dimethylamino)ethyl methacrylate] (star PDMAEMA) with different molecular weight were prepared. Riboflavin was used as a model drug to evaluate the drug loading capacities and drug release behaviors of the semi-IPN structural hydrogels. The molecular weight of the star PDMAEMA polymers was calculated by GPC, and the formation of semi-IPN structure was confirmed by FTIR and SEM. It was found that the molecular weight of star PDMAEMA has significant effect on the structure, swelling ratio and drug release behaviors of the semi-IPN hydrogel at different pH conditions. The results suggested that the PVA/star PDMAEMA-50,000 hydrogel exhibited highest swelling ratio and drug loading capacity. The pH-sensitive semi-IPN hydrogel based on star PDMAEMA could be a promising drug delivery system due to the controllable porous structure.

Robust Control of Microdomain Orientation in Thin Films of Block Copolymers by Zone Casting

Journal of the American Chemical Society. Aug, 2011  |  Pubmed ID: 21707027

Block copolymers with chemically immiscible segments exhibit a variety of microphase-separated nanostructures on the scale of 10-100 nm. Controlling the orientation of these microphase separated nanostructures is vital in many applications such as lithography, membranes, data storage, and so forth. Typical strategies involve the use of external fields or patterned substrates. Here, we report a robust zone casting technique to achieve highly ordered thin films of block copolymers on centimeter-scale substrates. The robustness of this technique is its powerful control on diverse morphologies and exceptional tolerance on versatility of block copolymer chemistry as well as allowance of a wide spectrum of substrates. We demonstrate that perpendicular orientations with respect to the surface are achieved for block copolymers with both lamellar and cylindrical morphologies by controlling solution casting rate, temperatures, and block copolymer chemical structures. Thin films of both noncrystalline and crystalline block copolymers exhibit excellent orientational order and lateral order. However, the lateral order in the thin films of crystalline block copolymers shows dependence on casting temperature and melting temperature of the crystalline segment. Remarkably, all the ordering is independent of the substrates on which the block copolymer films are cast.

Genomic Differences Distinguish the Myofibroblast Phenotype of Distal Lung Fibroblasts from Airway Fibroblasts

American Journal of Respiratory Cell and Molecular Biology. Dec, 2011  |  Pubmed ID: 21757679

Primary human distal lung/parenchymal fibroblasts (DLFs) exhibit a different phenotype from airway fibroblasts (AFs), including the expression of high levels of α-smooth muscle actin (α-SMA). The scope of the differences between these anatomically differentiated fibroblasts, or the mechanisms driving them, has remained unknown. To determine whether the different characteristics of regional fibroblasts are predicted by distinct genomic differences in AFs versus DLFs, matched human fibroblast pairs were isolated from proximal and distal lung tissue and evaluated. Microarray analysis was performed on 12 matched fibroblast pairs (four normal and eight asthmatic samples) and validated by quantitative real-time PCR. The potential functional implications of these differences were analyzed using computational approaches. Four hundred seventy-four transcripts were up-regulated in AFs, and 611 were up-regulated in DLFs via microarray analysis. No differences in normal and asthmatic fibroblasts were evident, and the data were combined for subsequent analyses. Gene ontology and network analyses suggested distinct patterns of pathway activation between AFs and DLFs. The up-regulation of extracellular matrix-associated molecules in AFs was observed, whereas genes associated with actin binding and cytoskeletal organization were up-regulated in DLFs. The up-regulation of activated/total SMAD3 and c-Jun N-terminal kinase in DLFs may partly explain these myofibroblast-like characteristics in DLFs. Thus, marked genomic differences exist between these two populations of regional lung fibroblasts. These striking differences may help identify potential mechanisms by which AFs and DLFs differ in their responses to injury, regeneration, and remodeling in the lung.

Linkage of Organic Anion Transporter-1 to Metabolic Pathways Through Integrated "omics"-driven Network and Functional Analysis

The Journal of Biological Chemistry. Sep, 2011  |  Pubmed ID: 21757732

The main kidney transporter of many commonly prescribed drugs (e.g. penicillins, diuretics, antivirals, methotrexate, and non-steroidal anti-inflammatory drugs) is organic anion transporter-1 (OAT1), originally identified as NKT (Lopez-Nieto, C. E., You, G., Bush, K. T., Barros, E. J., Beier, D. R., and Nigam, S. K. (1997) J. Biol. Chem. 272, 6471-6478). Targeted metabolomics in knockouts have shown that OAT1 mediates the secretion or reabsorption of many important metabolites, including intermediates in carbohydrate, fatty acid, and amino acid metabolism. This observation raises the possibility that OAT1 helps regulate broader metabolic activities. We therefore examined the potential roles of OAT1 in metabolic pathways using Recon 1, a functionally tested genome-scale reconstruction of human metabolism. A computational approach was used to analyze in vivo metabolomic as well as transcriptomic data from wild-type and OAT1 knock-out animals, resulting in the implication of several metabolic pathways, including the citric acid cycle, polyamine, and fatty acid metabolism. Validation by in vitro and ex vivo analysis using Xenopus oocyte, cell culture, and kidney tissue assays demonstrated interactions between OAT1 and key intermediates in these metabolic pathways, including previously unknown substrates, such as polyamines (e.g. spermine and spermidine). A genome-scale metabolic network reconstruction generated some experimentally supported predictions for metabolic pathways linked to OAT1-related transport. The data support the possibility that the SLC22 and other families of transporters, known to be expressed in many tissues and primarily known for drug and toxin clearance, are integral to a number of endogenous pathways and may be involved in a larger remote sensing and signaling system (Ahn, S. Y., and Nigam, S. K. (2009) Mol. Pharmacol. 76, 481-490, and Wu, W., Dnyanmote, A. V., and Nigam, S. K. (2011) Mol. Pharmacol. 79, 795-805). Drugs may alter metabolism by competing for OAT1 binding of metabolites.

Chemiluminescent Nanomicelles for Imaging Hydrogen Peroxide and Self-therapy in Photodynamic Therapy

Journal of Biomedicine & Biotechnology. 2011  |  Pubmed ID: 21765637

Hydrogen peroxide is a signal molecule of the tumor, and its overproduction makes a higher concentration in tumor tissue compared to normal tissue. Based on the fact that peroxalates can make chemiluminescence with a high efficiency in the presence of hydrogen peroxide, we developed nanomicelles composed of peroxalate ester oligomers and fluorescent dyes, called peroxalate nanomicelles (POMs), which could image hydrogen peroxide with high sensitivity and stability. The potential application of the POMs in photodynamic therapy (PDT) for cancer was also investigated. It was found that the PDT-drug-loaded POMs were sensitive to hydrogen peroxide, and the PDT drug could be stimulated by the chemiluminescence from the reaction between POMs and hydrogen peroxide, which carried on a self-therapy of the tumor without the additional laser light resource.

Flow-Dependent Regulation of Kruppel-Like Factor 2 Is Mediated by MicroRNA-92a

Circulation. Aug, 2011  |  Pubmed ID: 21768538

Upregulated by atheroprotective flow, the transcription factor Krüppel-like factor 2 (KLF2) is crucial for maintaining endothelial function. MicroRNAs (miRNAs) are noncoding small RNAs that regulate gene expression at the posttranscriptional level. We examined the role of miRNAs, particularly miR-92a, in the atheroprotective flow-regulated KLF2.

Effect of Hydrophilically Functionalized Carbon Nanotubes on the Reinforcement of Water-borne Epoxy Resin

Journal of Nanoscience and Nanotechnology. Jun, 2011  |  Pubmed ID: 21770160

Multi-walled carbon nanotubes (MWNTs) were modified covalently with hydrophilic polyacrylic acid (PAA) oligomer. Fourier transform infrared (FTIR), thermogravimetric (TG) analysis, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were used to characterize the modified MWNTs. The solubility of the modified MWNTs in water was determined to be 55.6 mg/mL by UV/vis spectroscopy. They could be dispersed homogeneously in water-borne epoxy resin and improve the mechanical properties of the resin significantly. The reinforcing ability of the modified MWNTs should be contributed by the fine dispersion of the MWNTs in resin matrix and the robust covalent binding formed by the carbon nanotube-bound carboxylic acid and epoxy groups in the resin.

Astrocyte Activation but Not Neuronal Impairment Occurs in the Hippocampus of Mice After 2 Weeks of D-galactose Exposure

Life Sciences. Sep, 2011  |  Pubmed ID: 21784081

The objective of this study is to prove that activation of astrocytes precedes neuron cell death in the neurodegenerative process induced by d-galactose (d-gal) exposure.

Sensing or No Sensing: Can the Anomeric Effect Be Probed by a Sensing Molecule?

Journal of the American Chemical Society. Aug, 2011  |  Pubmed ID: 21793584

The anomeric effect plays a central role in carbohydrate chemistry, but its origin is controversial, and both the hyperconjugation model and the electrostatic model have been proposed to explain this phenomenon. Recently, Cocinero et al. designed a peptide sensor, which can bind to a sugar molecule methyl D-galactose, and claimed that the anomeric effect can be sensed by the spectral changes from the β- to the α-complex, which are ultimately attributed to the lone pair electron density change on the endocyclic oxygen atom [Nature 2011, 469, 76; J. Am. Chem. Soc. 2011, 133, 4548]. Here, we provide strong computational evidence showing that the observed spectral changes simply come from the conformational differences between the α- and β-anomers, as the replacement of the endocyclic oxygen atom with a methylene group, which disables both the endo- and the exo-anomeric effects in methyl D-galactose, leads to similar spectral shifts. In other words, the "sensor" cannot probe the anomeric effect as claimed. We further conducted detailed energetic and structural analyses to support our arguments.

Combined Effect of Dark and Wounding on Regeneration Potential of Houttuynia Cordata Thunb. Leaves

Indian Journal of Experimental Biology. Jul, 2011  |  Pubmed ID: 21800505

Houttuynia cordata is one of the most potential medicinal and edible wild herb whose resources have decreased sharply due to excessive exploitation. Besides its slow agamic propagation, problems of browning and non-dedifferentiation have prevented the application of micropropagation in H. cordata. Through 4 week pre-culture in darkness and wounding after 1 week pre-culture, the browning rate of leaf explants decreased significantly and resulted in efficient regeneration (20.64 +/- 5.94 adventitious buds per explant) on the induction medium. The protocol shall facilitate conservation and commercial cultivation of the endangered species.

Determination of Nifeviroc, a Novel CCR5 Antagonist: Application to a Pharmacokinetic Study

Journal of Pharmaceutical and Biomedical Analysis. Nov, 2011  |  Pubmed ID: 21802236

Nifeviroc is a novel CCR5 antagonist used for the treatment of HIV type-1 infection. A LC-ESI-MS/MS method for the determination of nifeviroc in human plasma was developed and validated. The calibration curve (r(2)=0.9993) of nifeviroc was established at the range of 1.924-2935 μg L(-1). The intra- and inter-day precisions (RSD%) were all less than 7%, and the accuracies at three concentration levels were all within 100 ± 5%. This validated method was then successfully applied to a pharmacokinetic study in health Chinese volunteers.

[The Impact of PDTC on Circulating Tumor Cells of Laryngocarcinoma in Nude Mice Model]

Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi = Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery. May, 2011  |  Pubmed ID: 21805838

To investigate the correlation of the nuclear factor (NF-kappaB) and laryngocarcinoma circulating tumor cells (CTC), observe nuclear factor inhibitor PDTC on laryngeal cancer CTC and its possible mechanism.

Direct Imaging of Graphene Edges: Atomic Structure and Electronic Scattering

Nano Letters. Sep, 2011  |  Pubmed ID: 21806044

We report an atomically resolved scanning tunneling microscopy investigation of the edges of graphene grains synthesized on Cu foils by chemical vapor deposition. Most of the edges are macroscopically parallel to the zigzag directions of graphene lattice. These edges have microscopic roughness that is found to also follow zigzag directions at atomic scale, displaying many ∼120° turns. A prominent standing wave pattern with periodicity ∼3a/4 (a being the graphene lattice constant) is observed near a rare-occurring armchair-oriented edge. Observed features of this wave pattern are consistent with the electronic intervalley backscattering predicted to occur at armchair edges but not at zigzag edges.

[Effect of Different Fertilizing Levels on Yields and Efficiency Components of Pinellia Ternata from Sichuan]

Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica. Apr, 2011  |  Pubmed ID: 21809563

The effect of the different fertilizing levels on yields and main active components of Pinellia ternata from Sichuan was studied under the cultivated condition, in order to provide theoretical basis for the standardized cultivation.

Determination of Second-order Derivatives of a Skew Ray with Respect to the Variables of Its Source Ray in Optical Prism Systems

Journal of the Optical Society of America. A, Optics, Image Science, and Vision. Aug, 2011  |  Pubmed ID: 21811322

The second-order derivative of a scalar function with respect to a variable vector is known as the Hessian matrix. We present a computational scheme based on the principles of differential geometry for determining the Hessian matrix of a skew ray as it travels through a prism system. A comparison of the proposed method and the conventional finite difference (FD) method is made at last. It is shown that the proposed method has a greater inherent accuracy than FD methods based on ray-tracing data. The proposed method not only provides a convenient means of investigating the wavefront shape within complex prism systems, but it also provides a potential basis for determining the higher order derivatives of a ray by further taking higher order differentiations.

Expression of Carotenogenic Genes and Astaxanthin Production in Xanthophyllomyces Dendrorhous As a Function of Oxygen Tension

Zeitschrift Für Naturforschung. C, Journal of Biosciences. May-Jun, 2011  |  Pubmed ID: 21812346

This report gives an insight into the specific changes in the transcription of four key carotenogenic genes [encoding geranylgeranyl diphosphate synthase (crtE), phytoene desaturase (crtI), phytoene synthase lycopene cyclase (crtYB), and astaxanthin synthase (ast), respectively] in Xanthophyllomyces dendrorhous cultures, with regard to dissolved oxygen (DO) contents of 10%, 25%, and 40% air saturation, respectively. 25% DO proved to be the most beneficial for yeast growth, transcription of carotenogenic genes, and astaxanthin content.

Convergence of Cyclic and Almost-cyclic Learning with Momentum for Feedforward Neural Networks

IEEE Transactions on Neural Networks / a Publication of the IEEE Neural Networks Council. Aug, 2011  |  Pubmed ID: 21813357

Two backpropagation algorithms with momentum for feedforward neural networks with a single hidden layer are considered. It is assumed that the training samples are supplied to the network in a cyclic or an almost-cyclic fashion in the learning procedure, i.e., in each training cycle, each sample of the training set is supplied in a fixed or a stochastic order respectively to the network exactly once. A restart strategy for the momentum is adopted such that the momentum coefficient is set to zero at the beginning of each training cycle. Corresponding weak and strong convergence results are then proved, indicating that the gradient of the error function goes to zero and the weight sequence goes to a fixed point, respectively. The convergence conditions on the learning rate, the momentum coefficient, and the activation functions are much relaxed compared with those of the existing results.

The Min Oscillator Uses MinD-dependent Conformational Changes in MinE to Spatially Regulate Cytokinesis

Cell. Aug, 2011  |  Pubmed ID: 21816275

In E. coli, MinD recruits MinE to the membrane, leading to a coupled oscillation required for spatial regulation of the cytokinetic Z ring. How these proteins interact, however, is not clear because the MinD-binding regions of MinE are sequestered within a six-stranded β sheet and masked by N-terminal helices. minE mutations that restore interaction between some MinD and MinE mutants were isolated. These mutations alter the MinE structure leading to release of the MinD-binding regions and the N-terminal helices that bind the membrane. Crystallization of MinD-MinE complexes revealed a four-stranded β sheet MinE dimer with the released β strands (MinD-binding regions) converted to α helices bound to MinD dimers. These results identify the MinD-dependent conformational changes in MinE that convert it from a latent to an active form and lead to a model of how MinE persists at the MinD-membrane surface.

Liposomes Containing Glycocholate As Potential Oral Insulin Delivery Systems: Preparation, in Vitro Characterization, and Improved Protection Against Enzymatic Degradation

International Journal of Nanomedicine. 2011  |  Pubmed ID: 21822379

Oral delivery of insulin is challenging and must overcome the barriers of gastric and enzymatic degradation as well as low permeation across the intestinal epithelium. The present study aimed to develop a liposomal delivery system containing glycocholate as an enzyme inhibitor and permeation enhancer for oral insulin delivery.

[Effect of Ginsenoside Rg1 on the Spatial Learning-memory Ability in Dementia Rats After Transplanted with Bone Marrow Mesenchymal Stem Cells]

Zhongguo Zhong Xi Yi Jie He Za Zhi Zhongguo Zhongxiyi Jiehe Zazhi = Chinese Journal of Integrated Traditional and Western Medicine / Zhongguo Zhong Xi Yi Jie He Xue Hui, Zhongguo Zhong Yi Yan Jiu Yuan Zhu Ban. Jun, 2011  |  Pubmed ID: 21823427

To study the effect and mechanism of ginsenoside Rg1 on the spatial learning-memory ability in rats with Alzheimer's disease after transplanted with bone marrow mesenchymal stem cells (BMSCs).

Comparative Study on Antioxidant Capacity of Flavonoids and Their Inhibitory Effects on Oleic Acid-induced Hepatic Steatosis In Vitro

European Journal of Medicinal Chemistry. Sep, 2011  |  Pubmed ID: 21824690

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and its incidence is rising worldwide. We compared the antioxidant capacity of seventeen flavonoids with their inhibitory effects on oleic acid-induced triglyceride (TG) over-accumulation in HepG2 cells. The results showed significant correlations (P < 0.01) between the inhibition of intracellular TG levels and the suppression effects on reactive oxygen species. Nevertheless, the radical-reducing activities of flavonoids assessed by chemical assays (cyclic voltammetry and Folin-Ciocalteu reagent assay) were poorly correlated with their intracellular TG inhibitory effects. The relationships between structural properties of flavonoids and their inhibitory effects on TG over-accumulation were discussed.

Analysis of the Antioxidant Capacities of Flavonoids Under Different Spectrophotometric Assays Using Cyclic Voltammetry and Density Functional Theory

Journal of Agricultural and Food Chemistry. Sep, 2011  |  Pubmed ID: 21827150

Flavonoids often show inconsistent antioxidant activities (AAs) depending on the assay used. The electrochemical properties of 14 flavonoid standards in cyclic voltammetry [area under anodic wave (Q) and oxidant peak potentials (Epa)] and the structural parameters [bond dissociation enthalpy (BDE) and ionization potential (IP)] were investigated. They were compared with the results of four spectrophotometric assays, namely, diphenyl-1-picrylhydrazyl (DPPH), Folin-Ciocalteu reagent (FCR), ferric reducing ability of plasma (FRAP), Trolox equivalent antioxidant capacity (TEAC), to analyze the chemical reasons for the varying AAs of flavonoids under different assays. Using the cyclic voltammetry method, the AAs of the flavonoids in the DPPH, FCR, and FRAP assays were mainly determined by the ease of charge transferring in the first oxidation step. Meanwhile, the results of TEAC assays were primarily influenced by the amount of charge transfer in the multiple oxidation steps (MOS) of flavonoids. In the theoretical calculation, the BDE values of the selected flavonoids had considerably higher correlations with the results of the DPPH assay (r2=0.89) compared with the other three assays, which indicates that the oxidant-scavenging reaction of the tested flavonoids in the DPPH assay is closer to a hydrogen atom transfer mechanism. Neither the IP values nor BDE values had satisfactory correlation with the AAs of the flavonoids in the TEAC assay (r2=0.57, r2=0.54, respectively), Therefore, complex reaction mechanisms underlie this method and appropriate structural descriptors for reflecting the AAs of flavonoids based on MOS (e.g., TEAC values) need further investigation.

MicroRNA Let-7e Regulates the Expression of Caspase-3 During Apoptosis of PC12 Cells Following Anoxia/reoxygenation Injury

Brain Research Bulletin. Oct, 2011  |  Pubmed ID: 21827835

This study aimed to investigate the role and mechanism of action of microRNA (miR) let-7e in PC12 cells undergoing apoptosis following anoxia/reoxygenation (A/R) injury. The putative binding site of let-7e in the 3' UTR of caspase-3 (Casp3) mRNA was analyzed using the miRanda algorithm. Precursor let-7e (pre-miRNA), let-7e miR and anti-let-7e oligonucleotides were transfected into PC12 cells, which were then subjected to A/R injury. The levels of Casp3 mRNA and let-7e miRNA, the total protein levels of Casp3, Casp8 and Casp9 and levels of cellular apoptosis were measured. It was found that let-7e expression in PC12 cells was decreased, whereas the expression of Casp3 was significantly increased after A/R injury. The transfection of pre-miRNA or let-7e miR into PC12 cells decreased Casp3 expression levels and cellular apoptosis following A/R injury, while co-transfection of anti-let-7e strikingly alleviated the effects of let-7e miR. These results indicate that let-7e may protect PC12 cells against apoptosis following A/R injury by negatively regulating the expression of Casp3.

Mutations in Hepatitis B Virus DNA from Patients with Coexisting HBsAg and Anti-HBs

Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. Nov, 2011  |  Pubmed ID: 21840251

The serological markers with coexistence of hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs) of hepatitis B virus (HBV) infection were rare pattern. The virological significance, immune response and clinical outcome of these patients remain largely unknown.

The Use of Laminin Modified Linear Ordered Collagen Scaffolds Loaded with Laminin-binding Ciliary Neurotrophic Factor for Sciatic Nerve Regeneration in Rats

Biomaterials. Jun, 2011  |  Pubmed ID: 21397941

Nerve conduit provides a promising strategy for nerve injury repair in the peripheral nervous system (PNS). However, simply bridging the transected nerve with an empty conduit is hard to satisfy functional recovery. The regenerated axons may disperse during regeneration in the empty lumen, limiting the functional recovery. Our previous work had reported that linear ordered collagen scaffold (LOCS) could be used as a nerve guidance material. Here we cross-linked LOCS fibers with laminin which was a major component of the extracellular matrix in nervous system. Ciliary neurotrophic factor (CNTF) plays a critical role in peripheral nerve regeneration. But the lack of efficient CNTF delivery approach limits its clinical applications. To retain CNTF on the scaffold, a laminin binding domain (LBD) was fused to the N-terminal of CNTF. Compared with NAT-CNTF, LBD-CNTF exhibited specific laminin-binding ability and comparable neurotrophic bioactivity. We combined LBD-CNTF with the laminin modified LOCS fibers to construct a double-functional bio-scaffold. The functional scaffold was filled in silicon conduit and tested in the rat sciatic nerve transection model. Results showed that this functional biomaterial could guide the axon growth, retain more CNTF on the scaffolds and enhance the nerve regeneration as well as functional recovery.

Fever with Thrombocytopenia Associated with a Novel Bunyavirus in China

The New England Journal of Medicine. Apr, 2011  |  Pubmed ID: 21410387

Heightened surveillance of acute febrile illness in China since 2009 has led to the identification of a severe fever with thrombocytopenia syndrome (SFTS) with an unknown cause. Infection with Anaplasma phagocytophilum has been suggested as a cause, but the pathogen has not been detected in most patients on laboratory testing.

Transcriptomic Shock Generates Evolutionary Novelty in a Newly Formed, Natural Allopolyploid Plant

Current Biology : CB. Apr, 2011  |  Pubmed ID: 21419627

New hybrid species might be expected to show patterns of gene expression intermediate to those shown by parental species. "Transcriptomic shock" may also occur, in which gene expression is disrupted; this may be further modified by whole genome duplication (causing allopolyploidy). "Shock" can include instantaneous partitioning of gene expression between parental copies of genes among tissues. These effects have not previously been studied at a population level in a natural allopolyploid plant species. Here, we survey tissue-specific expression of 144 duplicated gene pairs derived from different parental species (homeologs) in two natural populations of 40-generation-old allotetraploid Tragopogon miscellus (Asteraceae) plants. We compare these results with patterns of allelic expression in both in vitro "hybrids" and hand-crossed F(1) hybrids between the parental diploids T. dubius and T. pratensis, and with patterns of homeolog expression in synthetic (S(1)) allotetraploids. Partitioning of expression was frequent in natural allopolyploids, but F(1) hybrids and S(1) allopolyploids showed less partitioning of expression than the natural allopolyploids and the in vitro "hybrids" of diploid parents. Our results suggest that regulation of gene expression is relaxed in a concerted manner upon hybridization, and new patterns of partitioned expression subsequently emerge over the generations following allopolyploidization.

A Hierarchical Bayesian Approach for Learning Sparse Spatio-temporal Decompositions of Multichannel EEG

NeuroImage. Jun, 2011  |  Pubmed ID: 21420499

Multichannel electroencephalography (EEG) offers a non-invasive tool to explore spatio-temporal dynamics of brain activity. With EEG recordings consisting of multiple trials, traditional signal processing approaches that ignore inter-trial variability in the data may fail to accurately estimate the underlying spatio-temporal brain patterns. Moreover, precise characterization of such inter-trial variability per se can be of high scientific value in establishing the relationship between brain activity and behavior. In this paper, a statistical modeling framework is introduced for learning spatio-temporal decompositions of multiple-trial EEG data recorded under two contrasting experimental conditions. By modeling the variance of source signals as random variables varying across trials, the proposed two-stage hierarchical Bayesian model is able to capture inter-trial amplitude variability in the data in a sparse way where a parsimonious representation of the data can be obtained. A variational Bayesian (VB) algorithm is developed for statistical inference of the hierarchical model. The efficacy of the proposed modeling framework is validated with the analysis of both synthetic and real EEG data. In the simulation study we show that even at low signal-to-noise ratios our approach is able to recover with high precision the underlying spatio-temporal patterns and the dynamics of source amplitude across trials; on two brain-computer interface (BCI) data sets we show that our VB algorithm can extract physiologically meaningful spatio-temporal patterns and make more accurate predictions than other two widely used algorithms: the common spatial patterns (CSP) algorithm and the Infomax algorithm for independent component analysis (ICA). The results demonstrate that our statistical modeling framework can serve as a powerful tool for extracting brain patterns, characterizing trial-to-trial brain dynamics, and decoding brain states by exploiting useful structures in the data.

Binary Higher Order Neural Networks for Realizing Boolean Functions

IEEE Transactions on Neural Networks / a Publication of the IEEE Neural Networks Council. May, 2011  |  Pubmed ID: 21427020

In order to more efficiently realize Boolean functions by using neural networks, we propose a binary product-unit neural network (BPUNN) and a binary pi-sigma neural network (BPSNN). The network weights can be determined by one-step training. It is shown that the addition " σ," the multiplication " π," and two kinds of special weighting operations in BPUNN and BPSNN can implement the logical operators " ∨," " ∧," and " ¬" on Boolean algebra 〈Z(2),∨,∧,¬,0,1〉 (Z(2)={0,1}), respectively. The proposed two neural networks enjoy the following advantages over the existing networks: 1) for a complete truth table of N variables with both truth and false assignments, the corresponding Boolean function can be realized by accordingly choosing a BPUNN or a BPSNN such that at most 2(N-1) hidden nodes are needed, while O(2(N)), precisely 2(N) or at most 2(N), hidden nodes are needed by existing networks; 2) a new network BPUPS based on a collaboration of BPUNN and BPSNN can be defined to deal with incomplete truth tables, while the existing networks can only deal with complete truth tables; and 3) the values of the weights are all simply -1 or 1, while the weights of all the existing networks are real numbers. Supporting numerical experiments are provided as well. Finally, we present the risk bounds of BPUNN, BPSNN, and BPUPS, and then analyze their probably approximately correct learnability.

Nanospheres-incorporated Implantable Hydrogel As a Trans-tissue Drug Delivery System

ACS Nano. Apr, 2011  |  Pubmed ID: 21428432

The objective of this study is to investigate the anticancer efficacy of a drug delivery system comprised of gelatin hydrogel (jelly) containing cisplatin (CDDP)-loaded gelatin/poly(acrylic acid) nanoparticles by peritumoral implantation and to compare the treatment response between the implantation administration of the jelly and intravenous (i.v.) administration of the nanoparticles. It is found that the implantation of the jelly containing CDDP-loaded nanoparticles on tumor tissue exhibited significantly superior efficacy in impeding tumor growth and prolonging the lifetime of mice than that of i.v. injection of CDDP-loaded nanoparticles in a murine hepatoma H(22) cancer model. An in vivo biodistribution assay performed on tumor-bearing mice demonstrated that the jelly implant caused much higher concentration and retention of CDDP in tumor and lower CDDP accumulation in nontarget organs than that of i.v. injected nanoparticles. Immunohistochemical analysis demonstrated that the nanoparticles from the jelly can be distributed in tumor tissue not only by their diffusion but also by the vasculature in the implantation region into tumor interior, enabling CDDP to efficiently reach more viable cells of tumor compared with i.v. injected nanoparticles. Thus, nanoparticles for peritumoral chemotherapy are promising for higher treatment efficacy due to increased tumor-to-normal organ drug uptake ratios and improved drug penetration in tumors.

A Facile Strategy for Constructing Boron-rich Polymer Nanoparticles Via a Boronic Acid-related Reaction

Macromolecular Rapid Communications. Mar, 2011  |  Pubmed ID: 21433212

We present here a facile strategy for constructing Dextran-poly(3-acrylamidophenylboronic acid) (Dextran-PAPBA) nanoparticles (NPs) through a radical polymerization of the monomer 3-acrylamidophenylboronic acid (APBA) bound by dextran via a boronic acid-diol reaction in aqueous solution. The synthesized Dextran-PAPBA NPs are stable in a wide pH range. Their size and composition are tunable by varying the feeding molar ratio of the glucopyranoside unit in dextran to APBA. Additionally, the NPs have good biocompatibility and cell membrane penetrability, as demonstrated by in vitro experiments. Doxorubicin was encapsulated in the NPs and exhibited a sustained and strongly pH-dependent release profile that would greatly favor the in vivo drug delivery performance of the NPs. The facility of this strategy together with the tunable boron content and outstanding drug release and cellular membrane crossing performance of the produced NPs should greatly boost their applications in boron neutron capture therapy (BNCT) and chemotherapy for cancer treatment.

Ginkgolide B Reduces Inflammatory Protein Expression in Oxidized Low-density Lipoprotein-stimulated Human Vascular Endothelial Cells

Journal of Cardiovascular Pharmacology. Jun, 2011  |  Pubmed ID: 21436722

Ginkgolide B is a herbal constituent extracted from leaves of the ginkgo biloba tree. Previous studies have shown that ginkgolide B is a specific platelet activating factor (PAF) receptor antagonist, and it suppresses PAF-mediated platelet activation via competitive binding. In this study, the effect of ginkgolide B on nicotinamide adenine dinucleotide phosphate oxidase and other inflammatory proteins in ox-LDL (low-density lipoprotein)-stimulated human vascular endothelial cells was investigated. Another PAF receptor antagonist CV3988 was employed to compare with ginkgolide B in this study. Our results show that the enhancement of Nox4 expression and reactive oxygen species generation was attenuated by ginkgolide B in cells treated with ox-LDL but not with CV3988. Increases in monocyte chemoattractant protein-1 and intercellular adhesion molecule 1 expression induced by ox-LDL, however, were inhibited by both ginkgolide B and CV3988. The translocation of NF-kappaB p65 (NF-κB) into the nucleus was inhibited by both ginkgolide B and CV3988. In conclusion, both ginkgolide B and CV3988 can inhibit the expression of inflammatory proteins by blocking NF-κB translocation. It seems that ginkgolide B possesses some pharmacological action on intracellular oxidative stress in association with the downregulation of Nox4 expression.

MiR-34a in Age and Tissue Related Radio-sensitivity and Serum MiR-34a As a Novel Indicator of Radiation Injury

International Journal of Biological Sciences. 2011  |  Pubmed ID: 21448283

MiR-34a, a direct target of p53, has shown to exert potent anti-proliferative effects. It has also been found that miR-34a can be induced by irradiation in vitro and in vivo. However, the relationship between miR-34a and radio-sensitivity, and its potential diagnostic significance in radiation biology, remain unclear. This study found that differing responses to ionizing radiation (IR) of young and adult mice were related to miR-34a. First, we found that miR-34a could be induced in many organs by radiation of both young and adult mice. However, the level of miR-34a induced by young mice was much higher when compared to adult mice. Next, we found that miR-34a played a critical role in radio-sensitivity variations of different tissues by enhancing cell apoptosis and decreasing cell viability. We also found that the induction of miR-34a by radiation was in a p53 dependent manner and that one possible downstream target of miR-34a that lead to different radio-sensitivity was the anti-apoptosis molecular Bcl-2. However, over-expression of miR-34a and knockdown of Bcl-2 could significantly enhance the radio-sensitivity of different cells while inhibition of miR-34a could protect cells from radiation injury. Finally, we concluded that miR-34a could be stable in serum after IR and serve as a novel indicator of radiation injury. Taken together, this data strongly suggests that miR-34a may be a novel indicator, mediator and target of radiation injury, radio-sensitivity and radioprotection.

Highly Sensitive Detection of HER2 Extracellular Domain in the Serum of Breast Cancer Patients by Piezoelectric Microcantilevers

Analytical Chemistry. May, 2011  |  Pubmed ID: 21449604

Rapid and sensitive detection of serum tumor biomarkers are needed to monitor cancer patients for disease progression. Highly sensitive piezoelectric microcantilever sensors (PEMS) offer an attractive tool for biomarker detection; however, their utility in the complex environment encountered in serum has yet to be determined. As a proof of concept, we have functionalized PEMS with antibodies that specifically bind to HER2, a biomarker (antigen) that is commonly overexpressed in the blood of breast cancer patients. The function and sensitivity of these anti-HER2 PEMS biosensors was initially assessed using recombinant HER2 spiked into human serum. Their ability to detect native HER2 present in the serum of breast cancer patients was then determined. We have found that the anti-HER2 PEMS were able to accurately detect both recombinant and naturally occurring HER2 at clinically relevant levels (>2 ng/mL). This indicates that PEMS-based biosensors provide a potentially effective tool for biomarker detection.

Artificial Niche Combining Elastomeric Substrate and Platelets Guides Vascular Differentiation of Bone Marrow Mononuclear Cells

Tissue Engineering. Part A. Aug, 2011  |  Pubmed ID: 21449713

Bone marrow-derived progenitor cells are promising cell sources for vascular tissue engineering. However, conventional bone marrow mesenchymal stem cell expansion and induction strategies require plating on tissue culture plastic, a stiff substrate that may itself influence cell differentiation. Direct scaffold seeding avoids plating on plastic; to the best of our knowledge, there is no report of any scaffold that induces the differentiation of bone marrow mononuclear cells (BMNCs) to vascular cells in vitro. In this study, we hypothesize that an elastomeric scaffold with adsorbed plasma proteins and platelets will induce differentiation of BMNCs to vascular cells and promote vascular tissue formation by combining soft tissue mechanical properties with platelet-mediated tissue repairing signals. To test our hypothesis, we directly seeded rat primary BMNCs in four types of scaffolds: poly(lactide-co-glycolide), elastomeric poly(glycerol sebacate) (PGS), platelet-poor plasma-coated PGS, and PGS coated by plasma supplemented with platelets. After 21 days of culture, osteochondral differentiation of cells in poly(lactide-co-glycolide) was detected, but most of the adhered cells on the surface of all PGS scaffolds expressed calponin-I and α-smooth muscle actin, suggesting smooth muscle differentiation. Cells in PGS scaffolds also produced significant amount of collagen and elastin. Further, plasma coating improves seeding efficiency, and platelet increases proliferation, the number of differentiated cells, and extracellular matrix content. Thus, the artificial niche composed of platelets, plasma, and PGS is promising for artery tissue engineering using BMNCs.

Food Protein-stabilized Nanoemulsions As Potential Delivery Systems for Poorly Water-soluble Drugs: Preparation, in Vitro Characterization, and Pharmacokinetics in Rats

International Journal of Nanomedicine. 2011  |  Pubmed ID: 21468355

Nanoemulsions stabilized by traditional emulsifiers raise toxicological concerns for long-term treatment. The present work investigates the potential of food proteins as safer stabilizers for nanoemulsions to deliver hydrophobic drugs. Nanoemulsions stabilized by food proteins (soybean protein isolate, whey protein isolate, β-lactoglobulin) were prepared by high-pressure homogenization. The toxicity of the nanoemulsions was tested in Caco-2 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide viability assay. In vivo absorption in rats was also evaluated. Food protein-stabilized nanoemulsions, with small particle size and good size distribution, exhibited better stability and biocompatibility compared with nanoemulsions stabilized by traditional emulsifiers. Moreover, β-lactoglobulin had a better emulsifying capacity and biocompatibility than the other two food proteins. The pancreatic degradation of the proteins accelerated drug release. It is concluded that an oil/water nanoemulsion system with good biocompatibility can be prepared by using food proteins as emulsifiers, allowing better and more rapid absorption of lipophilic drugs.

Up-regulation of MiR-21 Mediates Resistance to Trastuzumab Therapy for Breast Cancer

The Journal of Biological Chemistry. May, 2011  |  Pubmed ID: 21471222

Trastuzumab resistance emerges to be a major issue in anti-human epidermal growth factor receptor 2 (HER2) therapy for breast cancers. Here, we demonstrated that miR-21 expression was up-regulated and its function was elevated in HER2(+) BT474, SKBR3, and MDA-MB-453 breast cancer cells that are induced to acquire trastuzumab resistance by long-term exposure to the antibody, whereas protein expression of the PTEN gene, a miR-21 target, was reduced. Blocking the action of miR-21 with antisense oligonucleotides re-sensitized the resistant cells to the therapeutic activities of trastuzumab by inducing growth arrest, proliferation inhibition, and G(1)-S cell cycle checking in the presence of the antibody. Ectopic expression of miR-21 in HER2(+) breast cancer cells confers resistance to trastuzumab. Rescuing PTEN expression with a p3XFLAG-PTEN-mut construct with deleted miR-21 targeting sequence at its 3' UTR restored the growth inhibition of trastuzumab in the resistant cells by inducing PTEN activation and AKT inhibition. In vivo, administering miR-21 antisense oligonucleotides restored trastuzumab sensitivity in the resistant breast cancer xenografts by inducing PTEN expression, whereas injection of miR-21 mimics conferred trastuzumab resistant in the sensitive breast tumors via PTEN silence. Up-regulatin of miR-21 in tumor biopsies obtained from patients receiving pre-operative trastuzumab therapy was associated with poor trastuzumab response. Therefore, miR-21 overexpression contributes to trastuzumab resistance in HER2(+) breast cancers and antagonizing miR-21 demonstrates therapeutic potential by sensitizing the malignancy to anti-HER2 treatment.

Amelioration of Sepsis by Inhibiting Sialidase-mediated Disruption of the CD24-SiglecG Interaction

Nature Biotechnology. May, 2011  |  Pubmed ID: 21478876

Suppression of inflammation is critical for effective therapy of many infectious diseases. However, the high rates of mortality caused by sepsis attest to the need to better understand the basis of the inflammatory sequelae of sepsis and to develop new options for its treatment. In mice, inflammatory responses to host danger-associated molecular patterns (DAMPs), but not to microbial pathogen-associated molecular patterns (PAMPs), are repressed by the t interaction of CD24 and SiglecG (SIGLEC10 in human). Here we use an intestinal perforation model of sepsis to show that microbial sialidases target the sialic acid-based recognition of CD24 by SiglecG/10 to exacerbate inflammation. Sialidase inhibitors protect mice against sepsis by a mechanism involving both CD24 and Siglecg, whereas mutation of either gene exacerbates sepsis. Analysis of sialidase-deficient bacterial mutants confirms the key contribution of disrupting sialic acid-based pattern recognition to microbial virulence and supports the clinical potential of sialidase inhibition for dampening inflammation caused by infection.

[Preliminary Exploration into Chinese Medicine Treatment of Stenting in Coronary Heart Disease]

Zhongguo Zhong Xi Yi Jie He Za Zhi Zhongguo Zhongxiyi Jiehe Zazhi = Chinese Journal of Integrated Traditional and Western Medicine / Zhongguo Zhong Xi Yi Jie He Xue Hui, Zhongguo Zhong Yi Yan Jiu Yuan Zhu Ban. Mar, 2011  |  Pubmed ID: 21485064

[Research and Thinking of Hot Issues in Clinical Coronary Heart Disease]

Zhongguo Zhong Xi Yi Jie He Za Zhi Zhongguo Zhongxiyi Jiehe Zazhi = Chinese Journal of Integrated Traditional and Western Medicine / Zhongguo Zhong Xi Yi Jie He Xue Hui, Zhongguo Zhong Yi Yan Jiu Yuan Zhu Ban. Mar, 2011  |  Pubmed ID: 21485065

[1H Magnetic Resonance Spectroscopy in the Evaluation of High Intensity Focused Ultrasound Ablation for Primary Liver Cancer.]

Zhonghua Gan Zang Bing Za Zhi = Zhonghua Ganzangbing Zazhi = Chinese Journal of Hepatology. Feb, 2011  |  Pubmed ID: 21492511

To investigate the clinical value of 1H magnetic resonance spectroscopy (1H MRS) in the evaluation of high intensity focused ultrasound (HIFU) ablation for primary liver cancer. Routine magnetic resonance sequences, contrast-enhanced magnetic resonance imaging and respiratory-triggered single voxel point resolved spectroscopy sequence (PRESS) were performed on 24 patients with primary liver cancer before and after HIFU ablation. A respiratory-triggered axial T2 weighted imaging (T2WI) was used as localizer for PRESS. Spectroscopy data was transmitted to a personal computer and was post-processed with a custom software (Saker, provided by Ning Jing, an engineer in GE Healthcare). It would be considered "technical success" if the baselines of spectra were stable and main metabolites were without overlapping and could be identified. Integral areas of choline (Cho) peak at 3.2 parts per million (ppm) and lipid (Lip) peak at 1.3 ppm were measured, and the choline to lipid (Cho/Lip) ratios were calculated. The differences of areas of Cho, Lip peak and Cho/Lip ratios before and after HIFU ablation were compared by using paired samples t test, and a P value of less than 0.05 was considered statistically significant. The technical success rate of 1H-MRS was 87.50% (42/48). Integral areas of Cho peak and Lip peak of 20 patients with satisfied spectra were measured, and the Cho/Lip ratios were calculated. The Integral area of Cho peak decreased from 34 597+/-6 802 before HIFU ablation to 6 372+/-2 466 after HIFU ablation (t = 18.02, P less than 0.01). The Integral area of Lip peak increased from 147 948+/-16 317 before HIFU ablation to 149 069+/-16 345 after HIFU ablation (t = -15.11, P less than 0.01). The Cho/Lip ratio decreased from 0.23+/-0.03 before HIFU ablation to 0.04+/-0.02 after HIFU ablation (t = 25.32, P less than 0.01). 1H-MRS could provide information of metabolites changes of primary liver cancer after HIFU ablation and could be used as a complementary sequence to other magnetic resonance sequences to evaluate all around primary liver cancer after HIFU ablation.

Functional Maturation of Drug Transporters in the Developing, Neonatal, and Postnatal Kidney

Molecular Pharmacology. Jul, 2011  |  Pubmed ID: 21493727

Because renal function in newborns is immature, the pharmacokinetics of drugs administered to neonates vary significantly from adult patients. The establishment of drug transport systems is a key process in the functional maturation of the nephron. However, a thorough examination of the expression of the main drug transporters in the kidney throughout all stages of development (embryonic, postnatal, and mature) has yet to be carried out, and the functional (physiological) impact is not well understood. Using time-series microarray data, we analyzed the temporal behavior of mRNA levels for a wide range of SLC and ABC transporters in the rodent kidney throughout a developmental time series. We find dynamic increases between the postnatal and mature stages of development for a number of transporters, including the proximal tubule-specific drug and organic anion transporters (OATs) OAT1 (SLC22a6) and OAT3 (SLC22a8). The OATs are the major multispecific basolateral drug, toxin, and metabolite transporters in the proximal tubule responsible for handling of many drugs, as well as the prototypical OAT substrate para-aminohippurate (PAH). We therefore performed specific in vivo pharmacokinetic analysis of the transport of PAH in postnatal and maturing rodent kidney. We show that there is a 4-fold increase in PAH clearance during this period. Clearance studies in Oat1 and Oat3 knockouts confirm that, as in the adult, Oat1 is the principle transporter of PAH in the postnatal kidney. The substantial differences observed supports the need for better understanding of pharmacokinetics in the newborn and juvenile kidney compared with the adult kidney at the basic and clinical level.

Synthesis of Oxygen-deficient Luminescent Mesoporous Silica Nanoparticles for Synchronous Drug Delivery and Imaging

Chemical Communications (Cambridge, England). Jul, 2011  |  Pubmed ID: 21499640

Oxygen-deficient luminescent mesoporous silica nanoparticles with uniform morphology/size and integrated mesoporosity-luminescent property in a single nanoparticle are successfully synthesized by a bottom-up self-assembly route followed by a post-calcination process, and can be used to facilely load/deliver drugs into cells and luminescently image cells.

Atomic-scale Investigation of Graphene Grown on Cu Foil and the Effects of Thermal Annealing

ACS Nano. May, 2011  |  Pubmed ID: 21500843

We have investigated the effects of thermal annealing on ex-situ chemically vapor deposited submonolayer graphene islands on polycrystalline Cu foil at the atomic-scale using ultrahigh vacuum scanning tunneling microscopy. Low-temperature annealed graphene islands on Cu foil (at ∼430 °C) exhibit predominantly striped Moiré patterns, indicating a relatively weak interaction between graphene and the underlying polycrystalline Cu foil. Rapid high-temperature annealing of the sample (at 700-800 °C) gives rise to the removal of Cu oxide and the recovery of crystallographic features of the copper that surrounds the intact graphene. These experimental observations of continuous crystalline features between the underlying copper (beneath the graphene islands) and the surrounding exposed copper areas revealed by high-temperature annealing demonstrates the impenetrable nature of graphene and its potential application as a protective layer against corrosion.

[Effect of Brucine on Secretion Function and Proliferation Capability of T Lymphocytes in Patients with Aplastic Anemia]

Zhongguo Shi Yan Xue Ye Xue Za Zhi / Zhongguo Bing Li Sheng Li Xue Hui = Journal of Experimental Hematology / Chinese Association of Pathophysiology. Apr, 2011  |  Pubmed ID: 21518503

The aim of this study was to investigate the effect of brucine on secretion of TNF-α, IFN-γ, IL-4 and proliferation of T lymphocytes in patients with aplastic anemia (AA), and to explore its mechanism. Peripheral blood T lymphocytes from 10 patients with AA and 10 healthy volunteers were isolated, purified and cultured. T lymphocytes from the patients were divided into 0, 100, 200 and 400 µg/ml brucine-treated groups. T lymphocytes from healthy volunteers were used as control group. After being cultured for 72 hours, the levels of TNF-α, IFN-γ, IL-4 in the supernatant of cultured T lymphocytes from AA patients were detected by ELISA, and the proliferation of T lymphocytes from AA patients was detected by MTT. The results showed that compared with the normal control group, the levels of TNF-α and IFN-γ in the culture supernatant significantly increased, and IL-4 was significantly decreased. The levels of TNF-α and IFN-γ in the culture supernatant of brucine treated groups were lower, and were dependent on the concentration of brucine. However, the levels of IL-4 were found to be not obviously changed. The inhibition rate of T lymphocytes in 100, 200 and 400µg/ml brucine-treated groups were (13.61 ± 4.31)%, (14.28 ± 4.31)% and (15.12 ± 4.56)% respectively, among which the differences were not statistically significant. It is concluded that the brucine can reduce the levels of TNF-α and IFN-γ through inhibiting the proliferation of T lymphocytes in AA patients, which provides experimental basis for therapy of AA patients.

[Expression of T-bet and Its Regulation on CD4(+) T Cell Polarization in Aplastic Anemia]

Zhongguo Shi Yan Xue Ye Xue Za Zhi / Zhongguo Bing Li Sheng Li Xue Hui = Journal of Experimental Hematology / Chinese Association of Pathophysiology. Apr, 2011  |  Pubmed ID: 21518527

Aplastic anemia (AA) is an autoimmune disease which take hematopoietic tissue as target cells. T lymphocyte-mediated cellular immune abnormality plays a key role in the pathogenesis of AA. Increase and hyperfunction of Thl lymphocytes are main feature of AA disease. The recent studies indicated that T-bet is Th1 cell-specific transcription factor, is crucial factor for polarization of CD4(+) T lymphocytes to Th1. High expression of T-bet in AA patients is an important link in pathogenesis of AA. In this article, T-bet and its relation with AA, including expression of T-bet in AA patients, the regulation of T-bet on polarization of CD4(+) T lymphocytes are reviewed.

MicroRNAs Patents: the Road from Bench to Bedsides for Cancer Treatment

Recent Patents on DNA & Gene Sequences. Aug, 2011  |  Pubmed ID: 21529336

MicroRNAs are a class of non-coding small RNAs, which posttranscriptionally regulate gene expression through mainly binding to 3' untranslated region of mRNA. Most microRNAs are evolutionally conserved cross species; whereas, novel microRNAs expressed in different organisms are also identified with next generation sequencing technology. MicroRNAs play crucial roles in development, stem cells self-renewal, apoptosis and cell cycle. Aberrant microRNA expression in cancer and other diseases has been extensively investigated; the specific microRNAs have been developed for cancer diagnosis, prediction of drug-response and therapeutic outcome. Given the roles of microRNAs in pathophysiological conditions, it is conceivable that development of "miR-drugs" with different strategies (miR mimics, anti-miR, small molecule inhibitors of specific miRs) provides great hope to fight against cancer in combination of conventional treatment. In this review, the course of microRNA research to understand cancer biology is briefly introduced, the translation of miRNA studies from bench to bedside, particularly, microRNA implication in cancer with patents for diagnosis, prognosis will be described; the current status and challenges of "miR-drugs" development will be discussed.

Numerical Approach for Computing the Jacobian Matrix Between Boundary Variable Vector and System Variable Vector for Optical Systems Containing Prisms

Journal of the Optical Society of America. A, Optics, Image Science, and Vision. May, 2011  |  Pubmed ID: 21532684

The design of optical systems containing prisms is comparatively difficult since each prism may contain multiple boundary surfaces. Many geometrical optical merit functions have been proposed based on first-order derivatives of the geometrical quantities of the system with respect to the boundary variable vector X(i). However, transferring the computed quantities into the system variable vector X(sys) is still highly challenging. Accordingly, this study proposes a new numerical method for determining the Jacobian matrix between X(i) and X(sys) directly. The proposed methodology can be easily implemented in computer code and provides a potential basis for the future development of a numerical technique for computing the second-order derivatives of the geometrical quantities of an optical system.

Transmembrane Protein 198 Promotes LRP6 Phosphorylation and Wnt Signaling Activation

Molecular and Cellular Biology. Jul, 2011  |  Pubmed ID: 21536646

Wnt/β-catenin signaling is fundamental in embryogenesis and tissue homeostasis in metazoans. Upon Wnt stimulation, cognate coreceptors LRP5 and LRP6 ([LRP5/6] low-density lipoprotein receptor-related proteins 5 and 6) are activated via phosphorylation at key residues. Although several kinases have been implicated, the LRP5/6 activation mechanism remains unclear. Here, we report that transmembrane protein 198 (TMEM198), a previously uncharacterized seven-transmembrane protein, is able to specifically activate LRP6 in transducing Wnt signaling. TMEM198 associates with LRP6 and recruits casein kinase family proteins, via the cytoplasmic domain, to phosphorylate key residues important for LRP6 activation. In mammalian cells, TMEM198 is required for Wnt signaling and casein kinase 1-induced LRP6 phosphorylation. During Xenopus embryogenesis, maternal and zygotic tmem198 mRNAs are widely distributed in the ectoderm and mesoderm. TMEM198 is required for Wnt-mediated neural crest formation, antero-posterior patterning, and particularly engrailed-2 expression in Xenopus embryos. Thus, our results identified TMEM198 as a membrane scaffold protein that promotes LRP6 phosphorylation and Wnt signaling activation.

[Inhibitory Effect of Hydroxysafflor Yellow A Against PMN Activation Induced by LPS]

Yao Xue Xue Bao = Acta Pharmaceutica Sinica. Feb, 2011  |  Pubmed ID: 21542285

Carthamus tinctorius L. is a traditional Chinese medicine with the effect of promoting blood circulation and removing blood stasis. HSYA (hydroxysafflor yellow A) is the main effective component of Carthamus tinctorius L. In order to study the inhibitory effects of HSYA against PMN (polymorphonuclear) activation induced by LPS (lipopolysaccharide), rabbit PMN adhesion potency which was activated by LPS through colorimetry method was observed. Cellular free calcium concentration was determined by fluorescence spectrophotometry. RT-PCR was applied to study the effect of HSYA on PMN TNF-alpha and IL-6 mRNA expression; The inhibition of HSYA on NF-kappaB activation was monitored with immunofluorescence. The results showed that after treated with HSYA, the increase of adhesion potency (HSYA dose 1.01 x 10(-4) mol x L(-1)), free calcium concentration (HSYA dose 3.1 x 10(-5) mol x L(-1)), TNF-alpha and IL-6 mRNA expression elevation (HSYA dose 5.2 x 10(-1) mol x L(-1)) induced by LPS were inhibited. HSYA can inhibit NF-kappaB p65 subgroup nuclear translocation (HSYA dose 5.2 x 10(-5) mol x L(-1)). It is suggested that HSYA is effective in PMN activation induced by LPS.

Thyroid Disruption by Di-n-butyl Phthalate (DBP) and Mono-n-butyl Phthalate (MBP) in Xenopus Laevis

PloS One. 2011  |  Pubmed ID: 21544203

Di-n-butyl phthalate (DBP), a chemical widely used in many consumer products, is estrogenic and capable of producing seriously reproductive and developmental effects in laboratory animals. However, recent in vitro studies have shown that DBP and mono-n-butyl phthalate (MBP), the major metabolite of DBP, possessed thyroid hormone receptor (TR) antagonist activity. It is therefore important to consider DBP and MBP that may interfere with thyroid hormone system.

Preparation and Characterization of Galactose-modified Liposomes by a Nonaqueous Enzymatic Reaction

Journal of Liposome Research. Sep, 2011  |  Pubmed ID: 21545336

In this study, NOH (NOH = N-octadecyl-4-[(D-galactopyranosyl)oxy]-2,3,5,6-tetrahydroxy hexanamide) was enzymatically synthesized as a targeting molecule and incorporated into liposomes to prepare a liposome surface modified with galactose. Glycyrrhetinic-acid-loaded liposome (GA-LP) and glycyrrhetinic-acid-loaded liposome surface modified with galactose (NOH-GA-LP) were prepared by the ethanol-injection method. NOH-GA-LP was characterized by morphology, particle size, zeta potential, encapsulation efficiency, release in vitro, and stability. The size of spherical particles was in the range of 179-211 nm. Spherical particles exhibit a positive electrical charge (38.7 mV) and possess high encapsulation efficiency (91.3%) and show sustained release (72% over 48 hours) in vitro. This novel approach for the liposome surface modified with galactose by enzymatic synthesis is expected to provide potential application as a drug carrier for active targeted delivery to hepatocytes.

Effect of Telbivudine Therapy on the Cellular Immune Response in Chronic Hepatitis B

Antiviral Research. Jul, 2011  |  Pubmed ID: 21549152

Weak T-cell reactivity to the hepatitis B virus (HBV) is believed to be the dominant cause of chronic HBV infection. Several lines of experimental evidence suggest that treatment with telbivudine increases the rate of HBV e antigen (HBeAg) loss, undetectable HBV DNA, and normalization of serum alanine aminotransferase (ALT) in chronic hepatitis B patients (CHB). However, it is still unclear how early antiviral therapy affects cellular immune responses during sustained telbivudine treatment. In order to investigate this issue, we measured detailed prospective clinical, virological, and biochemical parameters, and we examined the frequency of T cell subgroups as well as the ability of peripheral blood mononuclear cells (PBMC) to respond to stimuli at five protocol time points for 51 CHB patients who received telbivudine therapy for one year. The preliminary data from this study revealed that effective-treated patients showed an increased frequency of peripheral blood CD4(+)T lymphocytes, an augmented proliferative response of HBV-specific T-cells to the hepatitis B core antigen (HBcAg), and the induction of cytokines, such as interferon gamma (IFN-γ), tumour necrosis factor alpha (TNF-α) release at the site of infection compared to non-responsive patients. Enhanced HBV-specific T-cell reactivity to telbivudine therapy, which peaked at treatment week 12, was confined to a subgroup of effective-treated patients who achieved greater viral suppression.

Control and Characterization of Individual Grains and Grain Boundaries in Graphene Grown by Chemical Vapour Deposition

Nature Materials. Jun, 2011  |  Pubmed ID: 21552269

The strong interest in graphene has motivated the scalable production of high-quality graphene and graphene devices. As the large-scale graphene films synthesized so far are typically polycrystalline, it is important to characterize and control grain boundaries, generally believed to degrade graphene quality. Here we study single-crystal graphene grains synthesized by ambient chemical vapour deposition on polycrystalline Cu, and show how individual boundaries between coalescing grains affect graphene's electronic properties. The graphene grains show no definite epitaxial relationship with the Cu substrate, and can cross Cu grain boundaries. The edges of these grains are found to be predominantly parallel to zigzag directions. We show that grain boundaries give a significant Raman 'D' peak, impede electrical transport, and induce prominent weak localization indicative of intervalley scattering in graphene. Finally, we demonstrate an approach using pre-patterned growth seeds to control graphene nucleation, opening a route towards scalable fabrication of single-crystal graphene devices without grain boundaries.

Dispersion-corrected Energy Decomposition Analysis for Intermolecular Interactions Based on the BLW and DDXDM Methods

The Journal of Physical Chemistry. A. Jun, 2011  |  Pubmed ID: 21557586

As the simplest variant of the valence bond (VB) theory, the block-localized wave function (BLW) method defines the intermediate electron-localized state self-consistently at the DFT level and can be used to explore the nature of intermolecular interactions in terms of several physically intuitive energy components. Yet, it is unclear how the dispersion interaction affects such a kind of energy decomposition analysis (EDA) as standard density functional approximations neglect the long-range dispersion attractive interactions. Three electron densities corresponding to the initial electron-localized state, optimal electron-localized state, and final electron-delocalized state are involved in the BLW-ED approach; a density-dependent dispersion correction, such as the recently proposed dDXDM approach, can thus uniquely probe the impact of the long-range dispersion effect on EDA results computed at the DFT level. In this paper, we incorporate the dDXDM dispersion corrections into the BLW-ED approach and investigate a range of representative systems such as hydrogen-bonding systems, acid-base pairs, and van der Waals complexes. Results show that both the polarization and charge-transfer energies are little affected by the inclusion of the long-range dispersion effect, which thus can be regarded as an independent energy component in EDA.

Dynamic Variations in the Peripheral Blood Lymphocyte Subgroups of Patients with 2009 Pandemic H1N1 Swine-origin Influenza A Virus Infection

Virology Journal. 2011  |  Pubmed ID: 21569236

Novel Influenza A (H1N1) is an acute respiratory infectious disease. Animal experiments indicated that when H1N1 virus infected early hosts, it showed strong CD4(+), CD8(+), and CD4(+)CD25(+) T cell reactions. The aim of this study was to investigate the dynamic fluctuations of the peripheral blood lymphocyte subgroups in patients infected with H1N1 swine-origin influenza A virus (S-OIV).

Genistein and Tyrphostin AG556 Inhibit Inwardly-rectifying Kir2.1 Channels Expressed in HEK 293 Cells Via Protein Tyrosine Kinase Inhibition

Biochimica Et Biophysica Acta. Aug, 2011  |  Pubmed ID: 21570948

Previous studies reported the controversial effects that protein tyrosine kinase (PTK) inhibition could induce an up-regulation or down-regulation of Kir2.1 current. The present study investigates how the recombinant human Kir2.1 channels are regulated by PTKs using whole-cell patch voltage-clamp, immunoprecipitation and Western blot, and mutagenesis approaches. We found that hKir2.1 current was reversibly inhibited by the broad spectrum PTK inhibitor genistein and the highly selective EGFR (epidermal growth factor receptor) kinase inhibitor AG556 in a concentration-dependent manner. The inhibition of hKir2.1 channels by genistein or AG556 was countered by the protein tyrosine phosphatase (PTP) inhibitor orthovanadate. Immunoprecipitation and Western blot analysis revealed that tyrosine phosphorylation level of Kir2.1 channels was reduced by genistein or AG556, and the reduction was significantly antagonized by orthovanadate. The mutation of Y242 dramatically reduced the inhibitory response to AG556. The results obtained in this study demonstrate that hKir2.1 channels are down-regulated by PTK inhibition, suggesting that EGFR kinase participates in the modulation of human cardiac excitability.

Impact of Geometry on the Performance of Memristive Nanodevices

Nanotechnology. Jun, 2011  |  Pubmed ID: 21572201

We examined the influence of memristor geometry on switching endurance by comparing ribbed and planar TiO(2)-based cross-point devices with 50 nm × 50 nm lateral dimensions. We observed that planar devices exhibited a factor of over four improvement in median endurance value over ribbed structures for otherwise identical structures. Our simulations indicated that the corners in the upper wires of the ribbed devices experienced higher current density and more heating during device forming and switching, and hence a shorter life time.

Objective Assessment of Multiresolution Fusion Algorithms for Context Enhancement in Night Vision: A Comparative Study

IEEE Transactions on Pattern Analysis and Machine Intelligence. May, 2011  |  Pubmed ID: 21576753

Comparison of image processing techniques is critically important in deciding which algorithm, method, or metric to use for enhanced image assessment. Image fusion is a popular choice for various image enhancement applications such as overlay of two image products, refinement of image resolutions for alignment, and image combination for feature extraction and target recognition. Since image fusion is used in many geospatial and night vision applications, it is important to understand these techniques and provide a comparative study of the methods. In this paper, we conduct a comparative study on twelve selected image fusion metrics over six multiresolution image fusion algorithms for two different fusion schemes and input images with distortion. The analysis can be applied to different image combination algorithms, image processing methods, and over a different choice of metrics that are of use to an image processing expert. The paper relates the results to an image quality measurement based on power spectrum and correlation analysis and serves as a summary of many contemporary techniques for objective assessment of image fusion algorithms.

An Information-geometric Framework for Statistical Inferences in the Neural Spike Train Space

Journal of Computational Neuroscience. Nov, 2011  |  Pubmed ID: 21584775

Statistical inferences are essentially important in analyzing neural spike trains in computational neuroscience. Current approaches have followed a general inference paradigm where a parametric probability model is often used to characterize the temporal evolution of the underlying stochastic processes. To directly capture the overall variability and distribution in the space of the spike trains, we focus on a data-driven approach where statistics are defined and computed in the function space in which spike trains are viewed as individual points. To this end, we at first develop a parametrized family of metrics that takes into account different warpings in the time domain and generalizes several currently used spike train distances. These new metrics are essentially penalized L ( p ) norms, involving appropriate functions of spike trains, with penalties associated with time-warping. The notions of means and variances of spike trains are then defined based on the new metrics when p = 2 (corresponding to the "Euclidean distance"). Using some restrictive conditions, we present an efficient recursive algorithm, termed Matching-Minimization algorithm, to compute the sample mean of a set of spike trains with arbitrary numbers of spikes. The proposed metrics as well as the mean spike trains are demonstrated using simulations as well as an experimental recording from the motor cortex. It is found that all these methods achieve desirable performance and the results support the success of this novel framework.

[Expression Features of Glypican-3 and Its Diagnostic and Differential Values in Hepatocellular Carcinoma]

Zhonghua Gan Zang Bing Za Zhi = Zhonghua Ganzangbing Zazhi = Chinese Journal of Hepatology. Apr, 2011  |  Pubmed ID: 21586223

To investigate the expression features of glypican-3 (GPC-3) and its diagnostic and differential values in hepatocellular carcinoma (HCC).

Solid Self-nanoemulsifying Cyclosporin A Pellets Prepared by Fluid-bed Coating: Preparation, Characterization and in Vitro Redispersibility

International Journal of Nanomedicine. 2011  |  Pubmed ID: 21589647

The objective of this study was to evaluate fluid-bed coating as a new technique to prepare a pellet-based solid self-nanoemulsifying drug delivery system (SNEDDS) using cyclosporin A as a model of a poorly water-soluble drug.

Oxidation of the Cysteine-rich Regions of Parkin Perturbs Its E3 Ligase Activity and Contributes to Protein Aggregation

Molecular Neurodegeneration. 2011  |  Pubmed ID: 21595948

Accumulation of aberrant proteins to form Lewy bodies (LBs) is a hallmark of Parkinson's disease (PD). Ubiquitination-mediated degradation of aberrant, misfolded proteins is critical for maintaining normal cell function. Emerging evidence suggests that oxidative/nitrosative stress compromises the precisely-regulated network of ubiquitination in PD, particularly affecting parkin E3 ligase activity, and contributes to the accumulation of toxic proteins and neuronal cell death.

Functional Consequences of Bidirectional Promoters

Trends in Genetics : TIG. Jul, 2011  |  Pubmed ID: 21601935

Several studies have shown that promoters of protein-coding genes are origins of pervasive non-coding RNA transcription and can initiate transcription in both directions. However, only recently have researchers begun to elucidate the functional implications of this bidirectionality and non-coding RNA production. Increasing evidence indicates that non-coding transcription at promoters influences the expression of protein-coding genes, revealing a new layer of transcriptional regulation. This regulation acts at multiple levels, from modifying local chromatin to enabling regional signal spreading and more distal regulation. Moreover, the bidirectional activity of a promoter is regulated at multiple points during transcription, giving rise to diverse types of transcripts.

Hot-spot Engineering in Polygonal Nanofinger Assemblies for Surface Enhanced Raman Spectroscopy

Nano Letters. Jun, 2011  |  Pubmed ID: 21604751

Multiparticle assemblies of nanoscale structures are the fundamental building blocks for powerful plasmonic devices. Here we show the controlled formation of polygonal metal nanostructure assemblies, including digon, trigon, tetragon, pentagon, and hexagon arrays, which were formed on top of predefined flexible polymer pillars that undergo self-coalescence, analogous to finger closing, with the aid of microcapillary forces. This hybrid approach of combining top-down fabrication with self-assembly enables the formation of complex nanoplasmonic structures with sub-nanometer gaps between gold nanoparticles. On comparison of the polygon-shaped assemblies, the symmetry dependence of the nanoplasmonic structures was determined for application to surface enhanced Raman spectroscopy (SERS), with the pentagonal assembly having the largest Raman enhancement for the tested molecules. Electromagnetic simulations of the polygonal structures were performed to visualize the field enhancements of the hot spots so as to guide the rational design of optimal SERS structures.

Development and Characterization of 18 EST-SSR Markers in Sonneratia Caseolaris

American Journal of Botany. Apr, 2011  |  Pubmed ID: 21613152

• Premise of the study: Sonneratia caseolaris, a typical mangrove species, is widely distributed in the Indo-West Pacific region. EST-SSR markers were developed for this species to examine its genetic diversity. • Methods and Results: A total of 18 EST-SSR primer pairs were designed based on the transcriptome sequences of S. caseolaris. Thirteen primer pairs showed polymorphism with one to three alleles per locus when assessed in two populations from China and Australia. The observed heterozygosity and expected heterozygosity ranged from 0 to 0.5000, and 0 to 0.5217 in the Hainan population, and from 0 to 0.2500, and 0 to 0.4891 in the Queensland population, respectively. Thirteen of the 18 primer sets identified in S. caseolaris can be successfully applied to its congener S. alba, and a much lower level of polymorphisms was observed in this widespread species. • Conclusions: These polymorphic EST-SSR markers for S. caseolaris are likely to be useful for future genetic diversity studies.

ECoG Based Cortical Function Mapping Using General Linear Model

Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference. Aug, 2011  |  Pubmed ID: 22254812

Electrocorticography (ECoG) is an emerging tool to map brain functions in the context of neurosurgical intervention. Previous mapping methods based on the event related power spectrum are prone to noise. To improve the robustness of cortical function mapping, general linear model (GLM), which has been widely used in the analysis of functional magnetic resonance imaging (fMRI) data, is applied to bandpass filtered ECoG signals from each electrode. For a specific task, electrodes with best fitting parameters of the signal are identified, and the statistical significance of the fitting is mapped on the standard 3D brain model to provide a personalized map of sensorimotor functions. With the analysis of four patients' data, the proposed approach yields consistent results with those obtained by electrical cortical stimulation (ECS), while showing promising performance against noise.

Design and Simulation of Printed Spiral Coil Used in Wireless Power Transmission Systems for Implant Medical Devices

Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference. Aug, 2011  |  Pubmed ID: 22255221

Printed Spiral Coil (PSC) is a coil antenna for near-field wireless power transmission to the next generation implant medical devices. PSC for implant medical device should be power efficient and low electromagnetic radiation to human tissues. We utilized a physical model of printed spiral coil and applied our algorithm to design PSC operating at 13.56 MHz. Numerical and electromagnetic simulation of power transfer efficiency of PSC in air medium is 77.5% and 71.1%, respectively. The simulation results show that the printed spiral coil which is optimized for air will keep 15.2% power transfer efficiency in human subcutaneous tissues. In addition, the Specific Absorption Ratio (SAR) for this coil antenna in subcutaneous at 13.56 MHz is below 1.6 W/Kg, which suggests this coil is implantable safe based on IEEE C95.1 safety guideline.

Integrating the Spatial Profile of the N200 Speller for Asynchronous Brain-computer Interfaces

Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference. Aug, 2011  |  Pubmed ID: 22255353

The N200 speller is a novel brain-computer interface (BCI) paradigm utilizing the overt attention effects on motion onset visual evoked potentials (mVEP). However, the asynchronous performance of the N200 BCI has not been fully explored. In this paper, a novel algorithm was proposed, integrating the spatial profile of the visual speller to provide a more precise description of the mVEP responses. Most importantly, only control state data were used in the algorithm to train a classifier which can detect the non-control state effectively. Using offline recorded data, the asynchronous performance of the proposed algorithm was shown to be significantly better than that of a similar algorithm without using the spatial information. The proposed algorithm can be used for developing a practical, asynchronous N200 BCI system.

Learning Event-related Potentials (ERPs) from Multichannel EEG Recordings: A Spatio-temporal Modeling Framework with a Fast Estimation Algorithm

Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference. Aug, 2011  |  Pubmed ID: 22255939

Extracting event-related potentials (ERPs) from multichannel EEG recordings remains a challenge due to the poor signal-to-noise ratio (SNR). This paper presents a multivariate statistical model of ERPs by exploiting the existing knowledge about their spatio-temporal properties. In particular, a computationally efficient algorithm is derived for fast model estimation. The algorithm, termed SIM, can be intuitively interpreted as maximizing the signal-to-noise ratio in the source space. Using both simulated and real EEG data, we show that the algorithm achieves excellent estimation performance and substantially outperforms a state-of-the-arts algorithm in classification accuracies in a P300 target detection task. The results demonstrate that the proposed modeling framework offers a powerful tool for exploring the spatio-temporal patterns of ERPs as well as learning spatial filters for decoding brain states.

[Expression of Structural and Non-structural Proteins of Severe Fever with Thrombocytopenia Syndrome Bunyavirus]

Bing Du Xue Bao = Chinese Journal of Virology / [bian Ji, Bing Du Xue Bao Bian Ji Wei Yuan Hui]. Nov, 2011  |  Pubmed ID: 22263262

Severe fever with thrombocytopenia syndrome bunyavirus (SFTSV) is a novel phlebovirus, causing a life-threatening illness associated with the symptoms of severe fever and thrombocytopenia syndrome. The sequence and structure of the genome have already been illustrated in previous study. However, the characteristics and function of the structure and non-structure proteins is still unclear. In this study, we identified the density of the purified SFTSV virions as 1.135 g/mL in sucrose solution. Using RT-PCR method, we amplified the full coding sequence of RNA dependent RNA polymerase(RdRp), glycoprotein precursor (M), glycoprotein n (Gn), glycoprotein c (Gc), nuclear protein (NP) and non structural protein (NSs) of SFTSV (strain HB29). Respectively inserted the target genes into eukaryotic expression vector pcDNA5/FRT or VR1012, the target protein in 293T cell were successfully expressed. By analyzing the SFTSV virions in SDS-PAGE and using recombinant viral proteins with SFTS patients sera in Western blotting and Immunofluorescent assay, the molecule weight of structure and non-structure proteins of SFTSV were defined. The study provides the first step to understand the molecular characteristics of SFTSV.

Association Between the XRCC3 Polymorphisms and Breast Cancer Risk: Meta-analysis Based on Case-control Studies

Molecular Biology Reports. Dec, 2011  |  Pubmed ID: 22161248

The previous published data on the association between X-ray repair cross-complementing group 3 (XRCC3) T241M, A4541G, and A17893G polymorphisms and breast cancer risk remained controversial. Hence, we performed a meta-analysis to investigate the association between breast cancer and XRCC3 T241M (21,910 cases and 23,961 controls), A4541G (9,633 cases and 10,994 controls), and A17893G polymorphisms (10,761 cases and 12,235 controls) in different inheritance models. When all the eligible studies were pooled into the meta-analysis of XRCC3 T241M polymorphism, significantly increased risk of breast cancer was observed in recessive model (odds' ratio [OR] = 1.10, 95% confidence interval [CI] = 1.04-1.16) and in additive model (OR = 1.10, 95% CI = 1.03-1.16). No significant association was found between A4541G polymorphism and breast cancer risk. When all the eligible studies were pooled into the meta-analysis of XRCC3 A17893G polymorphism, no significant association was found in any genetic model. Additionally, when one study was deleted in the sensitive analysis, the results of XRCC3 A17893G were changed in the additive model (OR = 0.90, 95% CI = 0.82-0.99) and dominant model (OR = 0.94, 95% CI = 0.89-0.99). In summary, this meta-analysis indicates that T241M polymorphism show an increased breast cancer risk and A17893G polymorphism may be associated with decreased breast cancer risk. A study with the larger sample size is needed to further evaluated gene-environment interaction on XRCC3 T241M, A4541G, and A17893G polymorphisms and breast cancer risk.

[Surveillance of Schistosomiasis in Caohui Village, Xinjian County, 2005 - 2010]

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi = Chinese Journal of Schistosomiasis Control. Aug, 2011  |  Pubmed ID: 22164872

The surveillance of schistosomiasis in a national schistosomiasis surveillance site, Caohui Village, Xinjian County, 2005-2010 showed that the infection rates of residents and livestock decreased to below 3% and 5%, respectively. However, the endemic situation was still of instability. Therefore, we should strengthen the comprehensive control measures including the control of infectious sources in the light of local conditions to control the schistosomiasis endemic situation.

Expression Characteristics of Hypoxia-inducible Factor-1α and Its Clinical Values in Diagnosis and Prognosis of Hepatocellular Carcinoma

Hepatitis Monthly. Oct, 2011  |  Pubmed ID: 22224081

Hypoxia-inducible factor-1 (HIF-1) is a ubiquitously expressed oxygen-regulated transcription factor composed of α and β subunits. HIF-1 activates the transcription of various genes including those involved in the formation and metastatic growth of hepatocellular carcinoma (HCC).

AICAR, a Small Chemical Molecule, Primes Osteogenic Differentiation of Adult Mesenchymal Stem Cells

The International Journal of Artificial Organs. Dec, 2011  |  Pubmed ID: 22198598

The chemical approach to controlling stem cell fates is emerging as a powerful tool, holding great promise in tissue engineering and regenerative medicine. Various small molecules have been demonstrated capable of modulating stem cell differentiation. In this paper, we studied the effects of 5-aminoimidazole-4-carboxamide-1-ß-riboside (AICAR), an activator of AMP-activated protein kinase (AMPK), on mesenchymal stem cells (MSCs). AICAR at high concentrations (1.0-2.0 mM) significantly inhibited proliferation of both human amnion-derived MSCs (hAMSCs) and rabbit bone marrow-derived MSCs (BM-MSCs). Most importantly, AICAR efficiently promoted the osteogenic differentiation of hAMSCs and BM-MSCs in both growth medium and osteogenic medium. However, Metformin, another AMPK activator, showed no such effects. Meanwhile, AICAR significantly inhibited adipogenic differentiation of hAMSCs and BM-MSCs. Our data suggests that AICAR represents a potent molecule, which can be applied in bone tissue regeneration.

[Clinical Evaluation on the Coaxial 1.8 Mm Microincision Cataract Surgery]

[Zhonghua Yan Ke Za Zhi] Chinese Journal of Ophthalmology. Oct, 2011  |  Pubmed ID: 22321500

To study and compare the outcomes of coaxial 1.8 mm microincision phacoemulsification with conventional coaxial 3 mm small-incision cataract surgery.

[A Comparison and Significance of Plasma Riboflavin Levels in Patients with Esophageal Squamous Cell Carcinoma Versus Linzhou Healthy Migrants in Changzhi of Shanxi]

Zhonghua Nei Ke Za Zhi [Chinese Journal of Internal Medicine]. Dec, 2011  |  Pubmed ID: 22333176

To study the relationship between plasma riboflavin levels and esophageal squamous cell carcinoma.

[Treatment with Rapid Acting Insulin Analogs in Children and Adolescents with Diabetes]

Zhonghua Er Ke Za Zhi. Chinese Journal of Pediatrics. Nov, 2011  |  Pubmed ID: 22336315

Downregulation of CNPase in a MeCP2 Deficient Mouse Model of Rett Syndrome

Neurological Research. Jan, 2012  |  Pubmed ID: 22334035

OBJECTIVES: To investigate the possible target genes of methyl-CpG-binding protein 2 (MeCP2) that contribute to Rett syndrome (RTT). METHODS: Brain tissues were taken from Mecp2(308/Y) mice or control mice and then subjected to real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR), immunohistochemical staining, and Western blot analysis for connexin (Cx)43, Cx45, Cx40, Cx32, 2,3-cyclic nucleotide 3-phosphohydrolase (CNPase), and glial fibrillary acidic protein (GFAP). RESULTS: The expression of CNPase in subcortical white matter and hippocampi was lower in RTT mice compared to control mice at both mRNA and protein levels. In contrast, the expression of Cx43, Cx40, Cx45, Cx32, or GFAP was not altered in RTT mice compared to control mice. CONCLUSION: The downregulation of CNPase expression in the brain may be a possible consequence of MECP2 gene mutation, and the indicated dysfunction of the oligodendrocytes in the subcortical white matter and hippocampi may be involved in RTT pathogenesis.

Comparative Study of Thin Sectional Anatomical Images from Chinese Visible Human Data Set and Computed Tomography Images of Superior Mediastinum

Clinical Anatomy (New York, N.Y.). Feb, 2012  |  Pubmed ID: 22334507

The structures of superior mediastinum and their spatial relationships are complex and difficult to master. This study aimed to compare visualization of the superior mediastinum based on computed tomography (CT) images and on the thin sections of the Chinese visible human (CVH) data set to provide a sectional anatomical basis for diagnostic imaging of superior mediastinal pathology. CVH sections of the mediastinum of a 35-year old male were compared with plain and enhanced CT images of a 45-year old male without apparent abnormalities in the upper chest. In addition, a three-dimensional model based on the CVH sections was compared with a model based on CT images. Although CT imaging is noninvasive and can be carried out in many individuals, its weakness is clearly the visualization of small soft tissue structures. In this respect, the sectional anatomical approach of the CVH images is complementary, as it visualizes these small soft tissue structures due to the higher resolution in the plain of sectioning and the color of the different structures in the section. Three-dimensional surface and volume rendering of reconstructions of the CVH data set can help medical students and less experienced thoracic surgeons to familiarize themselves with the topographic anatomy of the superior mediastinal structures and their spatial relationships, and thus with interpreting CT images of patients. Clin. Anat., 2012. © 2012 Wiley Periodicals, Inc.

Genotypic Variants at 2q33 and Risk of Esophageal Squamous Cell Carcinoma in China: A Meta-analysis of Genome-wide Association Studies

Human Molecular Genetics. Feb, 2012  |  Pubmed ID: 22323360

Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma. We conducted a meta-analysis of all single nucleotide polymorphisms (SNPs) that showed nominally significant p-values in two previously published genome-wide scans that included a total of 2961 esophageal squamous cell carcinoma cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P < 5 x 10(-8) and the strongest signal was rs13016963, with a combined odds ratio (95% confidence interval) of 1.29 (1.19-1.40) and P = 7.63 x 10(-10). An imputation analysis of 4304 SNPs at 2q33 suggested a single association signal and the strongest imputed SNP associations were similar to those from the genotyped SNPs. We conducted an ancestral recombination graph analysis with 53 SNPs to identify one or more haplotypes that harbor the variants directly responsible for the detected association signal. This showed that the five SNPs exist in a single haplotype along with 45 imputed SNPs in strong linkage disequilibrium and the strongest candidate was rs10201587, one of the genotyped SNPs. Our meta-analysis found genome-wide significant SNPs at 2q33 that map to the CASP8/ALS2CR12/TRAK2 gene region. Variants in CASP8 have been extensively studied across a spectrum of cancers with mixed results. The locus we identified appears to be distinct from the widely studied rs3834129 and rs1045485 SNPs in CASP8. Future studies of esophageal and other cancers should focus on comprehensive sequencing of this 2q33 locus and functional analysis of rs13016963 and rs10201587and other strongly correlated variants.

New Antitumor Compounds from Carya Cathayensis

Bioorganic & Medicinal Chemistry Letters. Jan, 2012  |  Pubmed ID: 22330636

A new lignan (7R,8S,8'R)-4,4',9-trihydroxy-7,9'-epoxy-8,8'-lignan, and three new phenolics, carayensin-A, carayensin-B, and carayensin-C, together with 13 known compounds were isolated from the shells of Carya cathayensis. Their chemical structures were established mainly by 1D and 2D NMR techniques and mass spectrometry. All the compounds were evaluated for cytotoxicity against several human tumor types including human colorectal cancer cell lines (HCT-116, HT-29), human lung cancer cell line (A549), and human breast cancer cell line (MCF-7). The compounds 1, 5, 6, and 16 are considered to be potential as antitumor agents, which could significantly inhibit the cancer cell growth in a dose-dependent manner.

Aspirin Inhibits the Production of Reactive Oxygen Species by Downregulating Nox4 and Inducible Nitric Oxide Synthase in Human Endothelial Cells Exposed to Oxidized Low-density Lipoprotein

Journal of Cardiovascular Pharmacology. Jan, 2012  |  Pubmed ID: 22217881

ABSTRACT: Aspirin has anti-thrombotic activity and is commonly used to protect patients from cardiovascular disease attacks. The present study investigated whether aspirin reduces reactive oxygen species (ROS) and proinflammatory proteins in oxidized low-density lipoprotein (ox-LDL)-stimulated human vascular endothelial cells (HUVECs). The results showed that aspirin attenuated ROS generation induced by ox-LDL and downregulated Nox4 and iNOS expression. Redox-sensitive transcription factor nuclear factor κB (NF-κB) was inactivated by aspirin, significantly preventing NF-κB p65 subunit translocation into the nucleus. The expression of the monocyte/macrophage chemotactic protein MCP-1 also decreased, but endothelial NOS (eNOS) expression increased in aspirin-treated cells. Aspirin ameliorated oxidative stress by downregulating Nox4 and iNOS and improved endothelial cell function by increasing eNOS expression. Thus, aspirin may possess protective effects against ox-LDL-induced endothelial cell injury.

Alternative Use of Isoflurane and Propofol Confers Superior Cardioprotection Than Using One of Them Alone in a Dog Model of Cardiopulmonary Bypass

European Journal of Pharmacology. Feb, 2012  |  Pubmed ID: 22222823

Our previous clinical study reported that isoflurane preconditioning and high-dose propofol posttreatment attenuated myocardial ischemia/reperfusion injury of patients in surgery with cardiopulmonary bypass (CPB). This study was designed to confirm this cardiac protection by use of a dog CPB model and to elucidate the related mechanism. Adult mongrel male dogs undergoing standard CPB were assigned into 4 groups: Sham group, Propofol group, Isoflurane (Iso) group and isoflurane in combination of propofol (pre-Iso+P) group. After induction, anesthesia was maintained with propofol (Propofol group), isoflurane (Iso group) or isoflurane preconditioning in combination with propofol posttreatment (pre-Iso+P group). After 2h cardiac arrest and CPB, aortic cross-clamping was released to allow 2h reperfusion. The results demonstrated that joint use of isoflurane and propofol facilitated cardiac functional recovery, improved myocardial oxygen utilization and decreased cardiac enzyme release. Also, the oxidative damage caused by ischemia/reperfusion injury was remarkably attenuated. Linear regression analysis showed that cardiac function performance and oxidative stress status were inversely correlated, indicating the improved cardiac function was in closed association with the attenuation of oxidative stress. In addition, the cardiac oxygen consumption (VO(2)) was found to be significantly associated with the above cardiac function and oxidative stress parameters, suggesting VO(2) was predictive for the levels of cardiac damage and oxidative stress. Therefore, we conclude that alternative use of isoflurane and propofol confers superior cardioprotection against postischemic myocardial injury and dysfunction, and this protection was probably mediated by attenuation of cardiac oxidative damage.

HGF-induced PKCζ Activation Increases Functional CXCR4 Expression in Human Breast Cancer Cells

PloS One. 2012  |  Pubmed ID: 22242160

The chemokine receptor CXCR4 and its ligand CXCL12 have been shown to mediate the metastasis of many malignant tumors including breast carcinoma. Interaction between hepatocyte growth factor (HGF) and the Met receptor tyrosine kinase mediates development and progression of cancers. HGF is able to induce CXCR4 expression and contributes to tumor cell invasiveness in breast carcinoma. However, the mechanism of the CXCR4 expression modulated by c-Met-HGF axis to enhance the metastatic behavior of breast cancer cells is still unclear. In this study, we found that HGF induced functional CXCR4 receptor expression in breast cancer cells. The effect of HGF was specifically mediated by PKCζ activity. After transfection with PKCζ-siRNA, the phosphorylation of PKCζ and CXCR4 was abrogated in breast cancer cells. Interference with the activation of Rac1, a downstream target of HGF, prevented the HGF-induced increase in PKCζ activity and CXCR4 levels. The HGF-induced, LY294002-sensitive translocation of PKCζ from cytosol to plasma membrane indicated that HGF was capable of activating PKCζ, probably via phosphoinositide (PI) 3-kinases. HGF treatment also increased MT1-MMP secretion. Inhibition of PKCζ, Rac-1 and phosphatidylinositol 3-kinase may attenuate MT1-MMP expression in cells exposed to HGF. Functional manifestation of the effects of HGF revealed an increased ability for migration, chemotaxis and metastasis in MDA-MB-436 cells in vitro and in vivo. Our findings thus provided evidence that the process of HGF-induced functional CXCR4 expression may involve PI 3-kinase and atypical PKCζ. Moreover, HGF may promote the invasiveness and metastasis of breast tumor xenografts in BALB/c-nu mice via the PKCζ-mediated pathway, while suppression of PKCζ by RNA interference may abrogate cancer cell spreading.

Role of Spinal Cord in Regulating Mouse Kidney: A Virally Mediated Trans-synaptic Tracing Study

Urology. Jan, 2012  |  Pubmed ID: 22245294

OBJECTIVE: To determine the spinal innervation and neuronal connections is important for studying renal metabolic responses. MATERIALS AND METHODS: In this study, the spinal cords of 10 adult male C57BL/6J strain mice were mapped retrograde using injections of pseudorabies virus (PRV)-614. The virus, injected into the kidney, was specifically transported to the spinal cord. RESULTS: At 5 days after injection of the PRV-614, PRV-614-positive cells were found in the intermediolateral cell column, the intercalates nucleus, or the central autonomic nucleus of spinal cord segments T4-L1, and most PRV-614-labeled cells were found in the T9 segment. CONCLUSION: Our results revealed neuroanatomical circuits between kidney and the spinal intermediolateral cell column neurons.

Small Surfactant-like Peptides Can Drive Soluble Proteins into Active Aggregates

Microbial Cell Factories. Jan, 2012  |  Pubmed ID: 22251949

ABSTRACT: BACKGROUND: Inactive protein inclusion bodies occur commonly in Escherichia coli (E. coli) cells expressing heterologous proteins. Previously several independent groups have found that active protein aggregates or pseudo inclusion bodies can be induced by a fusion partner such as a cellulose binding domain from Clostridium cellulovorans (CBDclos) when expressed in E. coli. More recently we further showed that a short amphipathic helical octadecapeptide 18A (EWLKAFYEKVLEKLKELF) and a short beta structure peptide ELK16 (LELELKLKLELELKLK) have a similar property. RESULTS: In this work, we explored a third type of peptides, surfactant-like peptides, for performing such a "pulling-down" function. One or more of three such peptides (L6KD, L6K2, DKL6) were fused to the carboxyl termini of model proteins including Aspergillus fumigatus amadoriase II (AMA, all three peptides were used), Bacillus subtilis lipase A (LipA, only L6KD was used, hereinafter the same), Bacillus pumilus xylosidase (XynB), and green fluorescent protein (GFP), and expressed in E. coli. All fusions were found to predominantly accumulate in the insoluble fractions, with specific activities ranging from 25% to 92% of the native counterparts. Transmission electron microscopic (TEM) and confocal fluorescence microscopic analyses confirmed the formation of protein aggregates in the cell. Furthermore, binding assays with amyloid-specific dyes (thioflavin T and Cong red) to the AMA-L6KD aggregate and the TEM analysis of the aggregate following digestion with protease K suggested that the AMA-L6KD aggregate may contain structures reminiscent of amyloids, including a fibril-like structure core. CONCLUSIONS: This study shows that the surfactant-like peptides L6KD and it derivatives can act as a pull-down handler for converting soluble proteins into active aggregates, much like 18A and ELK16. These peptide-mediated protein aggregations might have important implications for protein aggregation in vivo, and can be explored for production of functional biopolymers with detergent or other interfacial activities.

Control of Thickness Uniformity and Grain Size in Graphene Films for Transparent Conductive Electrodes

Nanotechnology. Jan, 2012  |  Pubmed ID: 22173552

Large-scale and transferable graphene films grown on metal substrates by chemical vapor deposition (CVD) still hold great promise for future nanotechnology. To realize the promise, one of the key issues is to further improve the quality of graphene, e.g., uniform thickness, large grain size, and low defects. Here we grow graphene films on Cu foils by CVD at ambient pressure, and study the graphene nucleation and growth processes under different concentrations of carbon precursor. On the basis of the results, we develop a two-step ambient pressure CVD process to synthesize continuous single-layer graphene films with large grain size (up to hundreds of square micrometers). Scanning electron microscopy and Raman spectroscopy characterizations confirm the film thickness and uniformity. The transferred graphene films on cover glass slips show high electrical conductivity and high optical transmittance that make them suitable as transparent conductive electrodes. The growth mechanism of CVD graphene on Cu is also discussed, and a growth model has been proposed. Our results provide important guidance toward the synthesis of high quality uniform graphene films, and could offer a great driving force for graphene based applications.

Association of the Methylenetetrahydrofolate Reductase Gene A1298C Polymorphism with Male Infertility: a Meta-analysis

Annals of Human Genetics. Jan, 2012  |  Pubmed ID: 22175540

Published data on the association between the methylenetetrahydrofolate reductase (MTHFR) gene A1298C (rs1801131) polymorphism and male infertility risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. In this meta-analysis, a total of seven case-control studies including 1633 cases and 1735 controls were selected to evaluate the possible association. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the additive model, dominant model, recessive model, and allele-frequency genetic model. In the overall analysis, the frequency of the C1298 allele (C vs. A) was significantly associated with susceptibility to male infertility (OR = 1.12, 95% CI = 1.00-1.26). A subgroup analysis of the subjects showed that MTHFR 1298C was associated with significant increased risk of azoospermia in homozygote comparison (CC vs. AA) and recessive mode (CC vs. AA/AC) (OR = 1.66 for CC vs. AA genotype; OR = 1.67 for CC vs. AA/AC genotype). However, no statistically significant increased risk of oligoasthenoteratozoospermia was found in any of the genetic models. In conclusion, this meta-analysis supports that the MTHFR A1298C polymorphism is capable of causing male infertility susceptibility, especially azoospermia.

Proteomic Analysis of Colorectal Cancer Metastasis: Stathmin-1 Revealed As a Player in Cancer Cell Migration and Prognostic Marker

Journal of Proteome Research. Feb, 2012  |  Pubmed ID: 22181002

Metastasis accounts largely for the high mortality rate of colorectal cancer (CRC) patients. In this study, we performed comparative proteome analysis of primary CRC cell lines HCT-116 and its metastatic derivative E1 using 2-D DIGE. We identified 74 differentially expressed proteins, many of which function in transcription, translation, angiogenesis signal transduction, or cytoskeletal remodeling pathways, which are indispensable cellular processes involved in the metastatic cascade. Among these proteins, stathmin-1 (STMN1) was found to be highly up-regulated in E1 as compared to HCT-116 and was thus selected for further functional studies. Our results showed that perturbations in STMN1 levels resulted in significant changes in cell migration, invasion, adhesion, and colony formation. We further showed that the differential expression of STMN1 correlated with the cells' metastatic potential in other paradigms of CRC models. Using immunohistochemistry, we also showed that STMN1 was highly expressed in colorectal primary tumors and metastatic tissues as compared to the adjacent normal colorectal tissues. Furthermore, we also showed via tissue microarray analyses of 324 CRC tissues and Kaplan-Meier survival plot that CRC patients with higher expression of STMN1 have poorer prognosis.

Modulation of Human Cardiac Transient Outward Potassium Current by EGFR Tyrosine Kinase and Src-family Kinases

Cardiovascular Research. Jan, 2012  |  Pubmed ID: 22198508

AIMS: The human cardiac transient outward K(+) current I(to) (encoded by Kv4.3 or KCND3) plays an important role in phase 1 rapid repolarization of cardiac action potentials in the heart. However, modulation of I(to) by intracellular signal transduction is not fully understood. The present study was therefore designed to determine whether/how human atrial I(to) and hKv4.3 channels stably expressed in HEK 293 cells are regulated by protein tyrosine kinases (PTKs). METHODS AND RESULTS: Whole-cell patch voltage-clamp, immunoprecipitation, western blotting, and site-directed mutagenesis approaches were employed in the present study. We found that human atrial I(to) was inhibited by the broad-spectrum PTK inhibitor genistein, the selective epidermal growth factor receptor (EGFR) kinase inhibitor AG556, and the Src-family kinases inhibitor PP2. The inhibitory effect was countered by the protein tyrosine phosphatase inhibitor orthovanadate. In HEK 293 cells stably expressing human KCND3, genistein, AG556, and PP2 significantly reduced the hKv4.3 current, and the reduction was antagonized by orthovanadate. Interestingly, orthovanadate also reversed the reduced tyrosine phosphorylation level of hKv4.3 channels by genistein, AG556, or PP2. Mutagenesis revealed that the hKv4.3 mutant Y136F lost the inhibitory response to AG556, while Y108F lost response to PP2. The double-mutant Y108F-Y136F hKv4.3 channels showed no response to either AG556 or PP2. CONCLUSION: Our results demonstrate that human atrial I(to) and cloned hKv4.3 channels are modulated by EGFR kinase via phosphorylation of the Y136 residue and by Src-family kinases via phosphorylation of the Y108 residue; tyrosine phosphorylation of the channel may be involved in regulating cardiac electrophysiology.

Rapid, Repeated, and Clustered Loss of Duplicate Genes in Allopolyploid Plant Populations of Independent Origin

Current Biology : CB. Feb, 2012  |  Pubmed ID: 22264605

The predictability of evolution is debatable, with recent evidence suggesting that outcomes may be constrained by gene interaction networks [1]. Whole-genome duplication (WGD; polyploidization-ubiquitous in plant evolution [2]) provides the opportunity to evaluate the predictability of genome reduction, a pervasive feature of evolution [3, 4]. Repeated patterns of genome reduction appear to have occurred via duplicated gene (homeolog) loss in divergent species following ancient WGD [5-9], with evidence for preferential retention of duplicates in certain gene classes [8-10]. The speed at which these patterns arise is unknown. We examined presence/absence of 70 homeologous loci in 59 Tragopogon miscellus plants from five natural populations of independent origin; this allotetraploid arose ∼80 years ago via hybridization between diploid parents and WGD [11]. Genes were repeatedly retained or lost in clusters, and the gene ontology categories of the missing genes correspond to those lost after ancient WGD in the same family (Asteraceae; sunflower family) [6] and with gene dosage sensitivity [8]. These results provide evidence that the outcomes of WGD are predictable, even in 40 generations, perhaps due to the connectivity of gene products [8, 10, 12]. The high frequency of single-allele losses detected and low frequency of changes fixed within populations provide evidence for ongoing evolution.

Enantioselective [4+2] Cycloadditions of 2-Vinyl-1 H-indoles with 3-Nitro-2 H-chromenes Catalyzed by a Zn(OTf)(2) /Bis(oxazoline) Complex: An Efficient Approach to Fused Heterocycles with a Quaternary Stereocenter

Chemistry, an Asian Journal. Jan, 2012  |  Pubmed ID: 22267282

There's a ringer: The asymmetric [4+2] cycloaddition reaction of 3-nitro-2H-chromenes with 1-benzyl-2-vinyl-1H-indoles catalyzed by Zn(OTf)(2) with bis(oxazoline) ligands offers a practical and efficient method to synthesize a variety of fused heterocycles bearing a quaternary stereocenter with good reaction efficiency (up to 94% yield) and excellent stereoselectivities (up to 96% ee, >95:5 d.r.).

VBEFP: A Valence Bond Approach That Incorporates Effective Fragment Potential Method

The Journal of Physical Chemistry. A. Feb, 2012  |  Pubmed ID: 22276645

An ab initio explicit solvation valence bond (VB) method, called VBEFP, is presented. The VBEFP method is one type of QM/MM approach in which the QM part of system is treated within the ab initio valence bond scheme and the solvent water molecules are accounted by the effective fragment potential (EFP) method, which is a polarized force field approach developed by Gordon et al. ( J. Chem. Phys. 1996 , 105 , 1968 ). This hybrid method enables one to take the first-solvation shell and heterogeneous solvation effects into account explicitly with VB wave function. Therefore, the nature of chemical bonding and the mechanism of chemical reactions with explicit solvent environments can be explored at the ab inito VB level. In this paper, the hydrated metal-ligand complexes [M(2+)L](H(2)O)(n) (M(2+): Mg(2+), Zn(2+); L: NH(3), CH(2)O) are studied by the VBEFP method. Resonance energy and bond order are computed, and the influence of the solvent coordination and hydrogen bonding to the metal-ligand bonding are explored in the paper.

Gelatinase-stimuli Strategy Enhances the Tumor Delivery and Therapeutic Efficacy of Docetaxel-loaded Poly(ethylene Glycol)-poly(ɛ-caprolactone) Nanoparticles

International Journal of Nanomedicine. 2012  |  Pubmed ID: 22287839

Nanoscale drug carriers have been extensively developed to improve drug therapeutic efficiency. However, delivery of chemotherapeutic agents to tumor tissues and cells has not been favorably managed. In this study, we developed a novel "intelligent" nanoparticle, consisting of a gelatinase-cleavage peptide with poly(ethylene glycol) (PEG) and poly(ɛ-caprolactone) (PCL)-based structure for tumor-targeted docetaxel delivery (DOC-TNPs). The docetaxel-loaded PEG-PCL nanoparticles (DOC-NPs) that did not display gelatinase-stimuli behaviors were used as a control. We found clear evidence that the DOC-TNPs were transformed by gelatinases, allowing drug release and enhancing the cellular uptake of DOC (P < 0.01). In vivo biodistribution study demonstrated that targeted DOC-TNPs could accumulate and remain in the tumor regions, whereas non-targeted DOC-NPs rapidly eliminated from the tumor tissues. DOC-TNPs exhibited higher tumor growth suppression than commercialized Taxotere(®) (docetaxel; Jiangsu Hengrui Medicine Company, Jiangsu, China) and DOC-NPs on hepatic H22 tumor model via intravenous administration (P < 0.01). Both in vitro and in vivo experiments suggest that the gelatinase-mediated nanoscale delivery system is promising for improvement of antitumor efficacy in various overexpressed gelatinase cancers.

Association Between the COMT Val158Met Polymorphism and Breast Cancer Risk: a Meta-analysis of 30,199 Cases and 38,922 Controls

Molecular Biology Reports. Feb, 2012  |  Pubmed ID: 22297695

Many studies have reported the role of COMT Val158Met with breast cancer risk, but the results remained controversial. In addition, previous meta-analysis on COMT Val158Met showed conflicting results. Hence, we performed a meta-analysis to investigate the association between breast cancer and COMT Val158Met (30,199 cases and 38,922 controls) in different inheritance models. When all the eligible studies were pooled into this meta-analysis, there was no evidence of significant association between breast cancer risk and COMT Val158Met polymorphism in any genetic model (dominant model: odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.94-1.04, P value of heterogeneity test [P (h)] = 0.009, I (2) = 36.9%; recessive model: OR = 0.97, 95% CI = 0.92-1.02, P (h) = 0.044, I (2) = 28.6%; additive model: OR = 0.98, 95% CI = 0.91-1.05, P (h) = 0.004, I (2) = 40.4%). However, significant between-study heterogeneity was detected in any genetic model. Hence, we performed the stratified analysis according to ethnicity, source of controls, menopausal status, and family history. In the stratified analysis by ethnicity significantly decreased breast cancer risk was observed in Caucasian population (recessive model: OR = 0.96, 95% CI = 0.92-1.00, P (h) = 0.419, I (2) = 3.1%). In conclusion, this meta-analysis indicates that COMT Val158Met polymorphism may be associated with decreased breast cancer risk in Caucasian population. However, a study with the larger sample size is needed to further evaluated gene-environment interaction on COMT Val158Met polymorphisms and breast cancer risk.

Reply to Comment on the Paper "An Efficient Algorithm for Energy Gradients and Orbital Optimization in Valence Bond Theory"

Journal of Computational Chemistry. Feb, 2012  |  Pubmed ID: 22298305

van Lenthe, Broer, and Rashid made comments on our 2009 paper [Song et al., J. Comput. Chem. 2009, 30, 399] by criticizing that we did not properly reference the work by Broer and Nieuwpoort in 1988 [Broer and Nieuwpoort, Theor. Chim. Acta. 1988, 73, 405], and we favorably compared our valence bond self-consistent field (VBSCF) algorithm with theirs. However, both criticisms are unjustified insignificant. The Broer-Nieuwpoort algorithm, properly cited in our paper, is for the evaluations of matrix elements between determinants of nonorthogonal orbitals. Stating that this algorithm "can be used for an orbital optimization" afterwards [van Lenthe et al., submitted] is not a plausible way to require more credits or even criticize others. While we stand by our statement that our algorithms scales at O(m(4) ) and van Lenthe et al.'s approximate Newton Raphson algorithm scales at O(mN(5) ) (here m and N are the numbers of basis functions and electrons), as we discussed in our original paper, it becomes obvious that any strict comparison among different algorithms is difficult, unproductive, and counteractive. © 2012 Wiley Periodicals, Inc.

Flavivirus Infection Induces Indoleamine 2,3-dioxygenase in Human Monocyte-derived Macrophages Via Tumor Necrosis Factor and NF-κB

Journal of Leukocyte Biology. Feb, 2012  |  Pubmed ID: 22301793

Infection with West Nile virus (WNV) via a mosquito bite results in local viral replication in the skin, followed by viremia. Thus, tissue macrophages are ideally located to prevent the dissemination of WNV throughout the host. The current study shows that WNV infection of human monocyte-derived macrophages (MDM) results in increased WNV mRNA, protein, and infectious virions at 24 h p.i. with a decline in titer after 48 h. Concomitant with viral control was the robust induction of indoleamine 2,3-dioxygenase (IDO) and resultant metabolism of L-tryptophan (L-Trp) to kynurenine. In WNV-exposed cultures, IDO protein was induced primarily in noninfected versus viral-infected MDM. Whereas WNV infection increased the production of IFN-α, IFN-β, and TNF, only antibody neutralization of TNF attenuated IDO expression and activity. WNV infection also activated NF-κB, and inhibition of this pathway with BMS-345541 abrogated IDO induction. Similar results were also obtained with MDM infected with the related flavivirus, Japanese encephalitis virus. Whereas IDO-mediated L-Trp metabolism can exhibit antiviral properties, inhibition of IDO activity in MDM with L-1-MT or the addition of excess L-Trp did not affect viral control. However, culturing MDM in L-Trp-deficient medium or overexpression of IDO in cells prior to infection significantly attenuated WNV replication, which was reversed by adding excess L-Trp. Together, these data support that although IDO is not required by MDM for the clearance of established viral infection, the spread of flavivirus infection is limited by IDO expressed in uninfected, neighboring cells.

Enhanced Dissolution, Stability and Physicochemical Characterization of ATRA/2-hydroxypropyl-β-cyclodextrin Inclusion Complex Pellets Prepared by Fluid-bed Coating Technique

Pharmaceutical Development and Technology. Feb, 2012  |  Pubmed ID: 22304703

The aim of this work was to prepare stable all-trans-retinoic acid (ATRA)/2-hydroxypropyl-β-cyclodextrin (HPCD) inclusion complex pellets with industrial feasible technology, the fluid-bed coating technique, using PVP K30 simultaneously as binder and reprecipitation retarder. The coating process was fluent with high coating efficiency. In vitro dissolution of the inclusion complex pellets in 5% w/v Cremopher EL solution was dramatically enhanced with no reprecipitation observed, and significantly improved stability against humidity (92.5% and 75% RH) and illumination (4500 lx ± 500 lx) was achieved by HPCD inclusion. Differential scanning calorimetry and powder X-ray diffractometry confirmed the absence of crystallinity of ATRA. Fourier transform-infrared spectrometry revealed interaction between ATRA and HPCD adding evidence on inclusion of ATRA moieties into HPCD cavities. Solid-state (13)C NMR spectrometry indicated possible inclusion of ATRA through the polyene chain, which was the main reason for the enhanced photostability. It is concluded that the fluid-bed coating technique has the potential use in the industrial preparation of ATRA/HPCD inclusion complex pellets.

Structural Insights into a Human Anti-IFN Antibody Exerting Therapeutic Potential for Systemic Lupus Erythematosus

Journal of Molecular Medicine (Berlin, Germany). Feb, 2012  |  Pubmed ID: 22307521

Increasing evidences suggest that the type I interferon α (IFNα) plays a critical role in the etiopathogenesis of systemic lupus erythematosus (SLE), which makes it a promising therapeutic target for the treatment of the disease. By screening a large size non-immune human antibody library, we have developed a human single-chain antibody (ScFv) AIFNα1bScFv01 and corresponding whole antibody AIFNα1bIgG01 to human interferon α1b (IFNα1b) with high specificity and high affinity. The IgG antibody could down-regulate the expression of ISG15 and IFIT-1 induced by either recombinant IFNα1b or naïve IFNα from SLE patients' sera, and reduced total serum IgG and IgM antibodies level in a pristane-primed lupus-like mouse model. The crystal structure of AIFNα1bScFv01-IFNα1b complex solved to 2.8 Å resolution revealed that both Pro26-Gln40 region in loop AB and Glu147-Arg150 region in helix E of IFNα1b contribute to binding with AIFNα1bScFv01. Four residues of above two regions (Leu30, Asp32, Asp35 and Arg150) are critical for the formation of antigen-antibody complexes. AIFNα1bScFv01 shares partial epitopes of IFNα1b with its receptor IFNAR2 but with much higher binding affinity to IFNα1b than IFNAR2. Thus, AIFNα1bIgG01 exhibits its neutralizing activity through competition with IFNAR2 to bind with IFNα and prevents the activation of IFNα-mediated signaling pathway. Our results highlight the potential use of the human antibody for modulating the activity of IFNα in SLE.

HPLC Assay and Pharmacokinetics and Tissue Distribution Study of Glycyrrhetinic Acid Liposomes Modified with Galactosylated Lipid

Journal of Liposome Research. Feb, 2012  |  Pubmed ID: 22313057

The aim of this study was to evaluate the pharmacokinetics and tissue distribution of the glycyrrhetinic acid (GA) liposome modified with galactosylated lipid (NOH-GA-LP), compared with GA conventional liposome (GA-LP) and GA solution in mice. The pharmacokinetics and biodistribution of liposomal and solution formulation of GA in mice were studied after intravenous administration. Plasma and tissues were treated using liquid-liquid extraction and determined using reversed-phase high-performance liquid chromatography. Results showed that the mean residence times of NOH-GA-LP (2.99-fold) and GA-LP (2.94-fold) were higher than that of the GA solution in plasma. NOH-GA-LP produced a drug concentration in the liver that was markedly higher than that in other tissues and was approximately 2.0- and 4.8-fold of that of GA-LP and GA solution, respectively. In conclusion, the NOH-GA-LP prepared in this study is a promising sustained-release and drug-targeting system for antitumor drugs.

Erratum: Amelioration of Sepsis by Inhibiting Sialidase-mediated Disruption of the CD24-SiglecG Interaction

Nature Biotechnology. 2012  |  Pubmed ID: 22318044

Does This Patient Have an Infection of a Chronic Wound?

JAMA : the Journal of the American Medical Association. Feb, 2012  |  Pubmed ID: 22318282

Chronic wounds (those that have not undergone orderly healing) are commonly encountered, but determining whether wounds are infected is often difficult. The current reference standard for the diagnosis of infection of a chronic wound is a deep tissue biopsy culture, which is an invasive procedure.

Increased Level of Soluble Syndecan-1 in Serum Correlates with Myocardial Expression in a Rat Model of Myocardial Infarction

Molecular and Cellular Biochemistry. Jan, 2012  |  Pubmed ID: 21842422

A candidate marker for ventricular remodeling after myocardial infarction (MI), syndecan-1 (Sdc1), has been shown to be upregulated in myocardial tissues. However, the clinical potential of this marker depends on the ability to obtain samples safely and noninvasively. Therefore, we investigated the expression of soluble Sdc1 in the serum of rats after MI. Anterior descending coronary arteries of Sprague-Dawley rats were ligated, and MI was confirmed by morphologic and physiologic methods. Rats that underwent surgery without ligation served as the control group. We analyzed the expression of Sdc1 mRNA by quantitative reverse-transcription polymerase chain reaction and that of Sdc1 protein by western blot in heart tissue from the MI border and compared it to the expression of soluble Sdc1 in serum. The myocardial levels of expression of Sdc1 mRNA and protein were very low in the sham group but increased significantly in the MI group (P<0.01). The expression of myocardial Sdc1 reached a peak at day 3 and declined gradually thereafter, although the levels at 14 days remained significantly higher than those in the sham group. The expression of soluble Sdc1 in the sera of the rats in the MI group followed a similar pattern and was linearly correlated with the expression of Sdc1 protein in the MI border zone (r=0.952, P<0.01). Soluble Sdc1 was also detected at low levels in normal rat serum. These results may facilitate additional exploration of the utility of serum Sdc1 as a biomarker for MI in humans.

The Scutellar Vascular Bundle-specific Promoter of the Wheat HD-Zip IV Transcription Factor Shows Similar Spatial and Temporal Activity in Transgenic Wheat, Barley and Rice

Plant Biotechnology Journal. Jan, 2012  |  Pubmed ID: 21689369

An HD-Zip IV gene from wheat, TaGL9, was isolated using a Y1H screen of a cDNA library prepared from developing wheat grain. TaGL9 has an amino acid sequence distinct from other reported members of the HD-Zip IV family. The 3' untranslated region of TaGL9 was used as a probe to isolate a genomic clone of the TaGL9 homologue from a BAC library prepared from Triticum durum L. cv. Langdon. The full-length gene containing a 3-kb-long promoter region was designated TdGL9H1. Spatial and temporal activity of TdGL9H1 was examined using promoter-GUS fusion constructs in transgenic wheat, barley and rice plants. Whole-mount and histochemical GUS staining patterns revealed grain-specific expression of TdGL9H1. GUS expression was initially observed between 3 and 8 days after pollination (DAP) in embryos at the globular stage and adjacent to the embryo fraction of the endosperm. Expression was strongest in the outer cell layer of the embryo. In developed wheat and barley embryos, strong activity of the promoter was only detected in the main vascular bundle of the scutellum, which is known to be responsible for the uptake of nutrients from the endosperm during germination and the endosperm-dependent phase of seedling development. Furthermore, this pattern of GUS staining was observed in dry seeds several weeks after harvesting but quickly disappeared during imbibition. The promoter of this gene could be a useful tool for engineering of early seedling vigour and protecting the endosperm to embryo axis pathway from pathogens during grain desiccation and storage.

SULT1A1 Arg213His Polymorphism and Susceptibility of Environment-related Cancers: a Meta Analysis of 5,915 Cases and 7,900 Controls

Molecular Biology Reports. Mar, 2012  |  Pubmed ID: 21670965

The common genetic polymorphism for SULT1A1 is Arg213His polymorphism, which may affect the sulfation process of various environmental carcinogens and thus is suggested to be related to susceptibility of several cancers. However, studies on the association between SULT1A1 Arg213His polymorphism and cancer susceptibility are inconsistent. To assess the relationship between Arg213His polymorphism and environmental-related cancers systematically, we performed a meta analysis from 20 case-control studies including 5,915 cases and 7,900 controls. The odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of risk, we found a significant association between SULT1A1 Arg213His polymorphism and environment-related cancers (for dominant model: OR 1.22, 95% CI 1.07-1.39, P = 0.003). When stratified by ethnicity, a significant risk was observed in Asian cases, compared with controls (for dominant model: OR 1.69, 95% CI 1.17-2.43, P = 0.005). When we chose only smokers in our analysis, we also found a significantly increased risk between Arg213His polymorphism and susceptibility of environment-related cancers for participants exposed to a smoking environment. In conclusion, SULT1A1 Arg213His polymorphism, ethnicity, smoking may modulate environment-related cancer risk. Studies on gene-gene interactions in the sequential or concurrent metabolic pathway and gene-environment interactions need to be further conducted to explore the susceptibility of cancer occurrence.

Effect of Cilostazol on the Progression of Carotid Intima-media Thickness: a Meta-analysis of Randomized Controlled Trials

Atherosclerosis. Jan, 2012  |  Pubmed ID: 22015232

It has been well established that cilostazol has anti-proliferative effect against in-stent restenosis. However, it remains unclear whether cilostazol can prevent the progression of carotid atherosclerosis.

A Novel Technique for Hepatic Progenitor Cell Isolation from Normal Adult Rat Livers

ASAIO Journal (American Society for Artificial Internal Organs : 1992). Jan-Feb, 2012  |  Pubmed ID: 22157072

The transplantation of hepatic progenitor cells (HPCs) is a promising alternate approach to liver transplantation for patients with end-stage liver disease. Here, we report a novel technique for HPCs isolation from normal adult rat livers (no preexposure to chemicals and no injury). HPCs were isolated from normal adult rat livers using a novel four-step collagenase perfusion method followed by density gradient centrifugation. The phenotypic properties of HPCs were characterized by morphological observation, reverse-transcription polymerase chain reaction (RT-PCR), and immunocytochemistry. The results showed that HPCs formed loose colonies and possessed a round or oval shape at culture day 3. These cells proliferated slowly and exhibited progenitor-like characteristics during the 30-day culture period. RT-PCR analysis indicated that the cultured cells were positive for several HPC-specific genes, such as albumin (ALB), alpha-fetoprotein (AFP), cytokeratin 18 (CK18), cytokeratin 19 (CK19), CD45, hepatocyte nuclear factor 1-alpha (HNF-1α), hepatocyte nuclear factor 4-alpha (HNF-4α), and Thy-1. Immunocytochemical staining showed that these cells were consistently positive for ALB, AFP, CK18, CK19, Thy-1, and OV-6. HPCs can be isolated from normal adult rat livers using a simple and effective technique involving four-step collagenase perfusion, further confirming their potential as a strong candidate for hepatocyte therapy.

Glycyrrhizin Attenuates Rat Ischemic Spinal Cord Injury by Suppressing Inflammatory Cytokines and HMGB1

Acta Pharmacologica Sinica. Jan, 2012  |  Pubmed ID: 22158106

To investigate the neuroprotective effect of glycyrrhizin (Gly) against the ischemic injury of rat spinal cord and the possible role of the nuclear protein high-mobility group box 1 (HMGB1) in the process.

Concurrent CIC Mutations, IDH Mutations, and 1p/19q Loss Distinguish Oligodendrogliomas from Other Cancers

The Journal of Pathology. Jan, 2012  |  Pubmed ID: 22072542

Oligodendroglioma is characterized by unique clinical, pathological, and genetic features. Recurrent losses of chromosomes 1p and 19q are strongly associated with this brain cancer but knowledge of the identity and function of the genes affected by these alterations is limited. We performed exome sequencing on a discovery set of 16 oligodendrogliomas with 1p/19q co-deletion to identify new molecular features at base-pair resolution. As anticipated, there was a high rate of IDH mutations: all cases had mutations in either IDH1 (14/16) or IDH2 (2/16). In addition, we discovered somatic mutations and insertions/deletions in the CIC gene on chromosome 19q13.2 in 13/16 tumours. These discovery set mutations were validated by deep sequencing of 13 additional tumours, which revealed seven others with CIC mutations, thus bringing the overall mutation rate in oligodendrogliomas in this study to 20/29 (69%). In contrast, deep sequencing of astrocytomas and oligoastrocytomas without 1p/19q loss revealed that CIC alterations were otherwise rare (1/60; 2%). Of the 21 non-synonymous somatic mutations in 20 CIC-mutant oligodendrogliomas, nine were in exon 5 within an annotated DNA-interacting domain and three were in exon 20 within an annotated protein-interacting domain. The remaining nine were found in other exons and frequently included truncations. CIC mutations were highly associated with oligodendroglioma histology, 1p/19q co-deletion, and IDH1/2 mutation (p < 0.001). Although we observed no differences in the clinical outcomes of CIC mutant versus wild-type tumours, in a background of 1p/19q co-deletion, hemizygous CIC mutations are likely important. We hypothesize that the mutant CIC on the single retained 19q allele is linked to the pathogenesis of oligodendrogliomas with IDH mutation. Our detailed study of genetic aberrations in oligodendroglioma suggests a functional interaction between CIC mutation, IDH1/2 mutation, and 1p/19q co-deletion.

Treatment with Selumetinib Preserves Cardiac Function and Improves Survival in Cardiomyopathy Caused by Mutation in the Lamin A/C Gene

Cardiovascular Research. Feb, 2012  |  Pubmed ID: 22068161

Mutations in A-type nuclear lamins gene, LMNA, lead to a dilated cardiomyopathy. We have reported abnormal activation of the extracellular signal-regulated kinase1/2 (ERK1/2) signalling in hearts from Lmna(H222P/H222P) mice, which develop dilated cardiomyopathy. We therefore determined whether an inhibitor of ERK1/2 signalling that has been investigated in clinical trials for cancer has the potential to be translated to humans with LMNA cardiomyopathy.

Draft Genome Sequence of Pigeonpea (Cajanus Cajan), an Orphan Legume Crop of Resource-poor Farmers

Nature Biotechnology. Jan, 2012  |  Pubmed ID: 22057054

Pigeonpea is an important legume food crop grown primarily by smallholder farmers in many semi-arid tropical regions of the world. We used the Illumina next-generation sequencing platform to generate 237.2 Gb of sequence, which along with Sanger-based bacterial artificial chromosome end sequences and a genetic map, we assembled into scaffolds representing 72.7% (605.78 Mb) of the 833.07 Mb pigeonpea genome. Genome analysis predicted 48,680 genes for pigeonpea and also showed the potential role that certain gene families, for example, drought tolerance-related genes, have played throughout the domestication of pigeonpea and the evolution of its ancestors. Although we found a few segmental duplication events, we did not observe the recent genome-wide duplication events observed in soybean. This reference genome sequence will facilitate the identification of the genetic basis of agronomically important traits, and accelerate the development of improved pigeonpea varieties that could improve food security in many developing countries.

Human Ether-à-go-go Gene Potassium Channels Are Regulated by EGFR Tyrosine Kinase

Biochimica Et Biophysica Acta. Feb, 2012  |  Pubmed ID: 22061963

Human ether á-go-go gene potassium channels (hEAG1 or Kv10.1) are expressed in brain and various human cancers and play a role in neuronal excitement and tumor progression. However, the functional regulation of hEAG channels by signal transduction is not fully understood. The present study was therefore designed to investigate whether hEAG1 channels are regulated by protein tyrosine kinases (PTKs) in HEK 293 cells stably expressing hEAG1 gene using whole-cell patch voltage-clamp, immunoprecipitation, Western blot, and mutagenesis approaches. We found that the selective epidermal growth factor receptor (EGFR) kinase inhibitor AG556 (10μM), but not the platelet growth factor receptor (PDGFR) kinase inhibitor AG1295 (10μM) or the Src-family inhibitor PP2 (10μM), can inhibit hEAG1 current, and the inhibitory effect can be reversed by the protein tyrosine phosphatase (PTP) inhibitor orthovanadate. Immunoprecipitation and Western blot analysis revealed that tyrosine phosphorylation level of hEAG1 channels was reduced by AG556, and the reduction was significantly countered by orthovanadate. The hEAG1 mutants Y90A, Y344A and Y485A, but not Y376A and Y479A, exhibited reduced response to AG556. Interestingly, the inhibition effect of AG556 was lost in triple mutant hEAG1 channels at Y90, Y344, and Y485 with alanine. These results demonstrate for the first time that hEAG1 channel activity is regulated by EGFR kinase at the tyrosine residues Tyr(90), Try(344), and Try(485). This effect is likely involved in regulating neuronal activity and/or tumor growth.

Comparative Study of the Effects of Solid-state Fermentation with Three Filamentous Fungi on the Total Phenolics Content (TPC), Flavonoids, and Antioxidant Activities of Subfractions from Oats (Avena Sativa L.)

Journal of Agricultural and Food Chemistry. Jan, 2012  |  Pubmed ID: 22136169

The aim of present work was to investigate the effect of solid-state fermentation with filamentous fungi (Aspergillus oryzae var. effuses, Aspergillus oryzae, and Aspergillus niger) on total phenolics content (TPC), flavonoids, and antioxidant activities of four subfractions of oat, namely, n-hexane, ethyl acetate (EA), n-butanol, and water, and compare them to their corresponding subfractions of unfermented oat. The TPC and total flavonoids increased dramatically, especially in EA subfractions (p < 0.05). The levels of antioxidant activity of subfractions were also significantly enhanced (p < 0.05). The highest antioxidant activities were also found in the EA subfractions. The polyphenols in EA were analyzed by high-performance liquid chromatography at 280 nm. Most polyphenols were increased remarkably, especially ferulic and caffeic acids. There was a clear correlation between the TPC and antioxidant activity. In conclusion, fungi fermentation is a potential bioprocess for increasing the TPC, flavonoids, and antioxidant activities of oat-based food.

Fluorescent Micelles Based on Star Amphiphilic Copolymer with a Porphyrin Core for Bioimaging and Drug Delivery

Macromolecular Bioscience. Jan, 2012  |  Pubmed ID: 22052617

Star-shaped poly(ε-caprolactone)-b-poly(ethylene oxide) amphiphilic copolymer with a tetrakis-(4-aminophenyl)-terminated porphyrin core was synthesized. Paclitaxel (PTX)-loaded polymeric micelles were prepared by the self-assembly of the star copolymer and in situ encapsulation of PTX. The fluorescent characteristic of the porphyrin moiety allowed the cellular uptake and biodistribution of the PTX-loaded micelles to be monitored by fluorescent imaging. The PTX-loaded micelles can be readily internalized by cancer cells and have a slightly higher cytotoxicity than clinic PTX injection Taxol. In vivo real-time fluorescent imaging revealed that the micelles could accumulate at tumor site via the blood circulation in tumor-bearing mice. In vivo antitumor efficacy examinations indicated that the PTX-loaded micelles had significantly superior efficacy in impeding tumor growth than Taxol and low toxicity to the living mice.

Association Between Occult Hepatitis B Infection and the Risk of Hepatocellular Carcinoma: a Meta-analysis

Liver International : Official Journal of the International Association for the Study of the Liver. Feb, 2012  |  Pubmed ID: 21745272

The association between occult hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) remains controversial.