The -149C>T polymorphism of DNMT3B is not associated with colorectal cancer risk: Evidence from a meta-analysis based on case-control studies.

The aim of this study was to examine the association between the -149C>T polymorphism of DNA methyltransferase 3B (DNMT3B) and colorectal cancer (CRC) susceptibility. A comprehensive search was conducted to identify all case-control studies of the -149C>T polymorphism of DNMT3B and CRC risk. Statistical analysis was performed with the software program Stata (version 12.

ARK5 promotes glioma cell invasion, and its elevated expression is correlated with poor clinical outcome.

Poor prognosis of malignant gliomas is primarily attributed to their highly invasive nature. Despite the identification of new biomarkers and molecular targets for the improvement of the diagnosis, prognosis and treatment of glioma, the overall prognosis of the disease remains poor. This study is the first to show the significant upregulation of ARK5 paraffin-embedded archival glioma biopsies compared with those in adjacent non-cancerous brain tissues.

Structure-based design of pyridopyrimidinediones as dipeptidyl peptidase IV inhibitors.

Dipeptidyl peptidase IV (DPP-4) inhibitors have been shown to enhance GLP-1 levels and thereby improve hyperglycemia in type II diabetes. From a small fragment hit, using structure-based design, we have discovered a new class of non-covalent, potent and selective DPP-4 inhibitors.

[Effects of phosphorous fertilizers on phytoavailability of cadmium in its contaminated soil and related mechanisms].

To explore an effective measure to ensure the safety of rice quality in cadmium (Cd)-contaminated farmland, a pot culture experiment was conducted to study the effects of of low Cd content (Cd < 0.2 mg x kg(-1)) phosphorous fertilizers with an application rate of 0.10 or 0.

Suppression of Tak1 promotes prostate tumorigenesis.

More than 30% of primary prostate cancers contain a consensus deletion of an approximately 800 kb locus on chromosome 6q15.1. The MAP3K7 gene, which encodes TGF-β activated kinase-1 (Tak1), is a putative prostate tumor suppressor gene within this region whose precise function remains obscure.

Design and synthesis of orally available MEK inhibitors with potent in vivo antitumor efficacy.

The structure-based design, synthesis, and biological evaluation of two novel series of potent and selective MEK kinase inhibitors are described herein. The elaboration of a lead pyrrole derivative to a bicyclic dihydroindolone core provided compounds with high potency and good drug-like pharmaceutical properties. Further scaffold modification afforded a series of dihydroindolizinone inhibitors, including an orally available advanced preclinical MEK inhibitor with potent in vivo antitumor efficacy.

Forced TR2/TR4 expression in sickle cell disease mice confers enhanced fetal hemoglobin synthesis and alleviated disease phenotypes.

Sickle cell disease (SCD) is a hematologic disorder caused by a missense mutation in the adult β-globin gene. Higher fetal hemoglobin (HbF) levels in red blood cells of SCD patients have been shown to improve morbidity and mortality. We previously found that nuclear receptors TR2 and TR4 repress expression of the human embryonic ε-globin and fetal γ-globin genes in definitive erythroid cells.

Ensemble neural activity of the frontal cortical basal ganglia system predicts reaction time task performance in rats.

The question pursued in this study was when neural activity appears in the cortico-basal ganglia system that could predict alternate behavioral responses in a reaction time (RT) task. In this protocol, rats first performed a nose poke to initiate a trial, depressed a lever when presented, and then released the lever after a tone cue. Multiple-channel, single-unit recordings (up to 62 units) were obtained simultaneously from the prefrontal cortex, the dorsal medial striatum, the globus pallidus, and the substantia nigra pars reticulata in a single rat during a session.

[Effects and mechanism of alkaline wastes application and zinc fertilizer addition on Cd bioavailability in contaminated soil].

The effects of paper mill sludge, red mud and zinc fertilizer addition on remediation of acid cadmium contaminated paddy soil were studied in a pot experiment, and their beneficial effects were verified in a field experiment, by using lime as comparison. The pot experiment results showed that a single application (2 g x kg(-1)) of lime, paper mill sludge or red mud increased soil pH significantly. Compared with no applying alkaline substances, the soil exchangeable Ca content was increased by 33.

Nuclear receptors TR2 and TR4 recruit multiple epigenetic transcriptional corepressors that associate specifically with the embryonic β-type globin promoters in differentiated adult erythroid cells.

Nuclear receptors TR2 and TR4 (TR2/TR4) were previously shown to bind in vitro to direct repeat elements in the mouse and human embryonic and fetal β-type globin gene promoters and to play critical roles in the silencing of these genes. By chromatin immunoprecipitation (ChIP) we show that, in adult erythroid cells, TR2/TR4 bind to the embryonic β-type globin promoters but not to the adult β-globin promoter. We purified protein complexes containing biotin-tagged TR2/TR4 from adult erythroid cells and identified DNMT1, NuRD, and LSD1/CoREST repressor complexes, as well as HDAC3 and TIF1β, all known to confer epigenetic gene silencing, as potential corepressors of TR2/TR4.

Discovery of TAK-733, a potent and selective MEK allosteric site inhibitor for the treatment of cancer.

A novel 5-phenylamino-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione series of MEK inhibitors has been developed using structure-based drug design. Lead optimization of this series led to the discovery of TAK-733. This was advanced to Phase I clinical studies for cancer treatment.

Design and synthesis of pyrimidinone and pyrimidinedione inhibitors of dipeptidyl peptidase IV.

The discovery of two classes of heterocyclic dipeptidyl peptidase IV (DPP-4) inhibitors, pyrimidinones and pyrimidinediones, is described. After a single oral dose, these potent, selective, and noncovalent inhibitors provide sustained reduction of plasma DPP-4 activity and lowering of blood glucose in animal models of diabetes. Compounds 13a, 27b, and 27j were selected for development.

Genome-wide binding of the orphan nuclear receptor TR4 suggests its general role in fundamental biological processes.

Background: The orphan nuclear receptor TR4 (human testicular receptor 4 or NR2C2) plays a pivotal role in a variety of biological and metabolic processes. With no known ligand and few known target genes, the mode of TR4 function was unclear.

Results: We report the first genome-wide identification and characterization of TR4 in vivo binding.

Structure-based design and synthesis of pyrrole derivatives as MEK inhibitors.

A novel series of pyrrole inhibitors of MEK kinase has been developed using structure-based drug design. Optimization of the series led to the identification of potent inhibitors with good pharmaceutical properties.

Light scattering induced by opposite microdomains in LiNbO3:Fe:Hf crystals.

We report on the light scattering phenomenon in annealed multidomain LiNbO3:Fe:Hf crystals. The scattering sources are found to be some fog-like "defects", which cause the polarization-dependent scattering of the light, and can be removed completely by the illumination of visible light. Based on these results and the etch patterns, these "defects" are suggested to be refractive index fluctuations induced by the space charges accumulated at the boundary of opposite microdomains.

Investigations on the UV photorefractivity of LiNbO(3):Hf.

The UV photorefractivity of LiNbO(3):Hf was investigated by beam distortion and two-wave coupling experiments. A sharp decrease of beam distortion was found between Hf concentrations of 2 and 2.5 mol.

[Therapeutic effect of anti-anaphylaxis granule on chronic urticaria and its impact on serum levels of RANTES].

Objective: To investigate the therapeutic effect of Anti-anaphylaxis Granule (AAG) on chronic urticaria and its impact on cytokine of regulated upon activation of normal T cells expressed and secreted (RANTES), eosinophil chemotactic factor (Eotaxin) and tumor necrosis factor-alpha (TNF-alpha).

Methods: The therapeutic effects of AAG and cetirizine on chronic urticaria patients allocated in two groups were observed respectively, and the serum levels of RANTES, Eotaxin and TNF-alpha in patients were measured by ELISA before and after treatment, and were compared with those in normal subjects.

Results: The therapeutic effects of AAG group were better in effective rate (88.

Determination of isocyanates by capillary electrophoresis with tris(2,2'-bipyridine)ruthenium(II) electrochemiluminescence.

CE with tris(2,2'-bipyridyl) ruthenium(II) (Ru(bpy)(3) (2+)) electrochemiluminescence (ECL) detection for the quantitative determination of isocyanates was first reported. Hexamethylene diisocyanate (HDI) and hexyl isocyanate (HI) were used as the model analytes. Commercially available N,N-diethyl-N'-methylethylenediamine was used as the derivatization reagent.

[Design and synthesis of 3'-methyl-furanonucleosides and their anti-tumor activities].

Taking 3'-Me-Ado (3'-methyladenosine) and Cladribine as the leading compounds, seventeen 3'-C-methyl-furanonucleosides were designed and synthesized. All the structures were confirmed by 1H NMR and MS. The target compounds were tested in vitro against human pulmonary carcinoma A549, human colon carcinoma LOVO and human leukemia CEM by MTT assay.

CEC with tris(2,2'-bipyridyl) ruthenium(II) electrochemiluminescent detection.

For the first time, CEC was coupled with tris(2,2-bipyridyl) ruthenium(II) (Ru(bpy)(3)(2+) electrochemiluminescence detection. Efficient CEC separations of proline, putrescine, spermidine and spermine were achieved when the pH of the mobile phase is in the range of 3.5-7.

Shugoshin1 may play important roles in separation of homologous chromosomes and sister chromatids during mouse oocyte meiosis.

Background: Homologous chromosomes separate in meiosis I and sister chromatids separate in meiosis II, generating haploid gametes. To address the question why sister chromatids do not separate in meiosis I, we explored the roles of Shogoshin1 (Sgo1) in chromosome separation during oocyte meiosis.

Methodology/principal Findings: Sgo1 function was evaluated by exogenous overexpression to enhance its roles and RNAi to suppress its roles during two meioses of mouse oocytes.

Hydrogen peroxide biosensor based on direct electrochemistry of soybean peroxidase immobilized on single-walled carbon nanohorn modified electrode.

Single-walled carbon nanohorns (SWCNHs) were used as a novel and biocompatible matrix for fabricating biosensing devices. The direct immobilization of acid-stable and thermostable soybean peroxidase (SBP) on SWCNH modified electrode surface can realize the direct electrochemistry of enzyme. Cyclic voltammogram of the adsorbed SBP displays a pair of redox peaks with a formal potential of -0.

Regulation of peripheral spindle movement and spindle rotation during mouse oocyte meiosis: new perspectives.

Spindle movement, including spindle migration during first meiosis and spindle rotation during second meiosis, is essential for asymmetric divisions in mouse oocytes. Previous studies by others and us have shown that microfilaments are required for both spindle migration and rotation. In the present study, we aimed to further investigate the mechanism controlling spindle movement during mouse oocyte meiosis.