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Aims Retinoic acid-inducible gene I-like receptors (RLRs) play an essential role in human innate immune, which may influence the spontaneous clearance of hepatitis B virus (HBV) infection. We aimed to investigate whether the SNPs in RLR family were associated with HBV spontaneous clearance. Methods The current study included 82 participants with spontaneous clearance, 601 asymptomatic hepatitis B surface antigen (HBsAg) carriers and 168 participants with chronic hepatitis B (CHB). Six SNPs (DDX58 rs3824456, rs3205166, DHX58 rs2074160, rs2074158, IFIH1 rs2111485, rs3747517) were genotyped to explore their association with HBV spontaneous clearance. Results Patients carrying the mutant allele C at rs3824456 or A at rs2074160 were more likely to achieve spontaneous clearance compared with asymptomatic HBsAg carriers (additive model: OR = 0.69, 95% CI = 0.49-0.97; dominant model: OR = 0.54, 95% CI = 0.31-0.95, respectively). In addition, patients carrying the mutant allele G at rs2111485 were more likely to achieve spontaneous clearance compared with CHB (dominant model: OR = 0.47, 95% CI = 0.25-0.87). The mutations were protective factors for HBV spontaneous clearance. Conclusion These results suggest the DDX58 rs3824456, DHX58 s2074160, IFIH1 rs2111485 were associated with spontaneous clearance of HBV, which may be predictive markers in the Chinese Han population of HBV. This article is protected by copyright. All rights reserved.

Serum B-cell maturation antigen (sBCMA) is a novel biomarker for B-cell malignancies. A normal reference range (

A highly emissive microgel is synthesized by polymerizing tetraphenylethene (TPE) based comonomers, acrylic acid, NIPAM, and permanent crosslinker ethylenebisacrylamide (BIS) (named as TPE microgel), which exhibited temperature responsive fluorescence emission. Rhodamine B (RhB), a positively charged molecule, is then inserted onto the surface of fabricated microgels through electrostatic interaction. As a result, a novel artificial light harvesting system with high energy transfer efficiency is constructed (named as TPE microgel-RhB light harvesting system), which is the first light harvesting system based on TPE microgels presenting dual response to pH and temperature. MTT assay indicates the fabricated TPE microgel and TPE microgel-RhB light harvesting system has good cytocompatibility. The strong fluorescence and good cytocompatibility make them perfect candidates for cell imaging. The prepared emissive microgel and light-harvesting system with desirable fluorescent property not only provide a new strategy for the fabrication of tunable luminescent nanomaterials, but also expand potential applications in the fields of stomach recognition, temperature sensors, and drug delivery.

Pogostone is an important constituent of Pogostemon cablin (Blanco) Benth., and possesses various known bioactivities. A rapid, simple and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the analysis of pogostone in rat plasma using chrysophanol as internal standard (IS). The analytes were extracted with methanol and separated using a reversed-phase YMC-UltraHT Pro C18 column. Elution was achieved with a mobile phase consisting of methanol–water (75:25, v/v) for 5 min at a flow rate of 400 μL/min. The precursor/product transitions (m/z) under MS/MS detection with negative electrospray ionization (ESI) were 223.0 139.0 and 253.1 224.9 for pogostone and IS, respectively. The calibration curve was linear over the concentration range 0.05–160 µg/mL (r = 0.9996). The intra- and inter-day accuracy and precision were within ±10%. The validated method was successfully applied to the preclinical pharmacokinetic investigation of pogostone in rats after intravenous (5, 10 and 20 mg/kg) and oral administration (5, 10 and 20 mg/kg). Finally, the oral absolute bioavailability of pogostone in rats was calculated to be 70.39, 78.18 and 83.99% for 5, 10 and 20 mg/kg, respectively. Copyright © 2013 John Wiley & Sons, Ltd.

Bipolar disorder (BD) is a chronic, severe psychiatric illness characterized by recurrent pathological swings of mood between mania and depression, often with catastrophic social, personal, medical, or vocational consequences. It is generally a lifetime diagnosis, with significant heterogeneity, that begins in late adolescence or early adulthood with variability in presentation, symptomatology and course of illness (1). The genetic predisposition to the illness and high heritability is observed clinically in family, twin, and adoption studies (2–4), and genetic linkage and association studies have found numerous modest risk loci for BD (5), consistent with a complex mode of inheritance in BD (6, 7). The currently reported genetic variants with modest odds ratios (1.1–1.3) cannot account for the high heritability of the disorder; additional approaches beyond population genetics will be needed to understand the etiology of BD. Gene expression analyses have used microarray technology to identify gene transcripts differentially expressed in postmortem brains or nucleated peripheral blood cells from BD affected individuals in comparison to healthy controls (8–16). Although these studies have identified sets of genes differentially expressed between BD samples and controls (Supplementary Table 1), each significant gene set identified was generally limited to a corresponding individual study. Few overlapping changes were consistent among the extant expression studies. A recent meta-analysis performed on 12 microarray data sets was performed to address the lack of consensus between studies (17), the results suggested that inconsistency between microarray studies was due to small sample size, overly restrictive or overly broad criteria for assigning of significance, as well as lack of consistent statistical adjustment for confounding effects. Meanwhile, the meta-analysis did identify 375 genes with significantly altered expression patterns in BD brains contrasting to controls. Many genes identified in this analysis are functionally related to energy processing, supporting an energy processing dysfunction hypothesis in BD (10, 17). Given the complex inheritance of BD and the current progress in gene mapping and expression analyses, we reason that findings from each independent study are likely to partially contribute to understanding the molecular basis of the illness. The integration and comparison of results from independent studies may prove helpful in the identification of genes and pathways for prioritization of deeper analyses. We compared the abundance of gene transcripts in brain samples from deceased individuals diagnosed with BD and unrelated controls, and identified transcripts with altered expression levels in BD brains (including many previous reported significant genes). When we used exposure to antipsychotic medication as a variable we find evidence that antipsychotics normalize the expression levels of genes in BD brains to near control levels.

Fast-swelling superabsorbent polymers (SAPs) have been prepared by micellar cross-linking copolymerization of acrylic acid and acrylamide using polymerizable macromolecular surfactants (PMSs) as multifunctional cross-linkers, with a foaming technique. Sodium bicarbonate (NaHCO3)/acetone and Pluronic F127 were used as foam (or porosity) generators and stabilizer, respectively. It has been found that the PMSs with different polyethylene glycol (PEG) chain length have little effect on the swelling rate of the SAPs, while the foam generators are crucial. In addition, the monomer concentration and the concentration of the PMS are important to the fast swelling rate of the SAPs. For a balance of a relatively fast-swelling rate, high water absorbency under load and low cost in drying, a monomer concentration of above 50%, 0.08% PMS, and 5% NaHCO3 are preferable. The water absorbency of SAP prepared under optimal conditions could reach half of equilibrium water absorbency in 30 seconds and the saline water absorbency under load could reach 18.4 g/g. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44173.

A novel curing agent, poly (amide-amidic acid) (PAA), was used to cure tetraglycidyl 4,4′-diaminodiphenylmethane (TGDDM). The initial cure and exothermic peak temperatures increased with increase in PAA content. The mechanism for the cure of TGDDM/PAA was proposed which involved, besides TGDDM cure, PAA imidization in the system. Examination of the morphology of the fractured surface using scanning electron microscopy showed that curing with PAA improved more the fracture toughness as compared to the conventional 4,4′-diaminodiphenylsulfone (DDS), and rendered TGDDM more fire resistant with higher char yield. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

Objectives: Examine the antitumor activity of the histone deacetylase inhibitor vorinostat’s antitumor activity against multiple myeloma (MM) using cell lines and a murine xenograft model. Methods: RPMI8226, U266, and MM1S cells were cultured for 48 h in the presence of media, vorinostat, melphalan, or bortezomib alone, or combinations of vorinostat with melphalan or bortezomib. Cell proliferation was measured using the MTS [3-(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfphophenyl)-2H-tetrazolium, inner salt] assay. Severe combined immunodeficient mice bearing LAGκ-1B tumors were treated with vorinostat [30, 60, or 100 mg/kg daily for five consecutive days per week (qd×5d), 100 or 300 mg/kg daily for 2 d/wk (qd×2d)], melphalan (1, 3, or 10 mg/kg qd×1d), bortezomib (0.25 or 0.5 mg/kg qd×2d), or combinations thereof for 35 d. Tumor growth was determined via measurement of human immunoglobulin G (hIgG) levels and tumor volume. Results and Conclusions: Vorinostat enhanced the anti-MM effects of melphalan and bortezomib in vitro. Synergism was observed with vorinostat and melphalan in RPMI8226 and U266 cell lines. Vorinostat 100 mg/kg in combination with melphalan 3 mg/kg resulted in significant inhibition of tumor growth in vivo, compared with control (tumor volume P = 0.0001; hIgG P = 0.0001), single-agent vorinostat (tumor volume P = 0.0025; hIgG P = 0.0137), and single-agent melphalan (tumor volume P = 0.0043; hIgG P = 0.0426). Vorinostat also enhanced the antimyeloma effects of bortezomib in vivo. Vorinostat enhances the anti-MM activity of melphalan and bortezomib in vitro and in vivo. This study provides rationale for further evaluation of vorinostat in combination with chemotherapeutic agents and bortezomib for the treatment of MM.

Arsenic trioxide (ATO) induces apoptosis of malignant plasma cells through multiple mechanisms, including inhibition of DNA binding by nuclear factor kappa-B, a key player in the development of chemoresistance in multiple myeloma (MM). This activity suggests that ATO may be synergistic when combined with other active antimyeloma drugs. To evaluate this, we examined the antimyeloma effects of ATO alone and in combination with bortezomib, melphalan and ascorbic acid (AA) both in vitro and in vivo using a severe combined immunodeficient (SCID)-hu murine myeloma model. Marked synergistic antimyeloma effects were demonstrated when human MM Los Angeles xenograft IgG lambda light chain (LAGlambda-1) cells were treated in vitro with ATO and any one of these agents. SCID mice bearing human MM LAGlambda-1 tumours were treated with single-agent ATO, bortezomib, melphalan, or AA, or combinations of ATO with either bortezomib or melphalan and AA. Animals treated with any of these drugs alone showed tumour growth and increases in paraprotein levels similar to control mice, whereas animals treated with ATO-containing combinations showed markedly suppressed tumour growth and significantly reduced serum paraprotein levels. These in vitro and in vivo results suggest that addition of ATO to other antimyeloma agents may result in improved outcomes for patients with relapsed or refractory MM.

Summary Pleiotrophin (PTN), a tightly regulated angiogenic and mitogenic heparin-binding protein, is markedly elevated in a variety of aggressive solid tumours. The role of PTN in haematological malignancies, however, has not been previously evaluated. This study demonstrated that PTN serum levels were elevated in multiple myeloma (MM) patients when compared with healthy subjects (P

TNF is a pleiotropic cytokine that modulates cell proliferation and apoptosis. The objective of the present study was to investigate the possible function(s) of the TNF/TNF-R1 signaling pathway in embryonic mouse submandibular salivary gland (SMG) morphogenesis. After characterizing in vivo mRNA and protein expression of various constituents of this pathway, we utilized in vitro experiments to investigate the phenotypic outcomes of enhanced and deficient ligand. The results of these experiments indicate that the TNF/TNF-R1 signal transduction pathway plays an important role in balancing cell proliferation and apoptosis during SMG duct and presumptive acini formation.

In this paper, polyetherimides (PEI) with two different calculated number-average molecular weights (Mn) of 5000 and 10,000 g/mol were synthesized and used to modify tetraglycidyl 4,4′-diaminodiphenylmethane. Three different morphologies (separated phase, bi-continuous phase, and phase inversion structure) were obtained by controlling molecular weights and content of PEI. Thermal and mechanical characterizations showed that addition of PEI resulted in an increase in thermal stability and tensile strength. Tensile strength of samples with bi-continuous phase was higher than those with separated phase or phase inversion structure. Influence of morphologies on tribology properties were studied by a ring-on-block wear tester. Higher wear resistance was achieved from samples with bi-continuous phase. It was found that wear life of samples with bi-continuous phase was almost 100% higher than that of samples with separated phase. This is clearly related to the change in thermal and mechanical properties caused by the change of morphologies. Scanning electron microscope observations of worn surfaces and wear debris of the tested samples showed that tribological behaviors and wear mechanisms were heavily dependent on morphologies. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 39863.

Glucocorticoids (CORT) have been shown to induce cleft palate in mice. Although the pathogenetic pathway of CORT-induced cleft palate has been investigated for several decades, the molecular details remain to be elucidated. Since growth factors have been shown to regulate palate morphogenesis, and the expression of several growth factors or their receptors, e.g. TGF-beta, EGF receptor (EGF-R), are known to be modulated by CORT, we postulate that CORT modulation of growth factor (or receptor) gene expression is a key mechanism involved in CORT-induced cleft palate. To test this hypothesis, we analyzed the steady-state levels (Northern and RNase protection) and developmental expression (in situ hybridization) of four CORT-responsive genes--TGF-Beta 1, TGF- beta 2, TGF-beta 3, and EGF receptor (EGF-R)--in developing mouse palates in the presence or absence of exogenous CORT. Pregnant B10.A dams were injected on day 12 of gestation with CORT or sham-injected and embryonic palates were collected at 1, 2, and 3 days postinjection (E13-E15). During mouse palate development, significant increases in TGF-beta 1 and TGF-beta 3 mRNA levels, as well as significant decrease in TGF-beta 2 mRNA levels, are detected; no significant difference in EGF-R transcript level is observed with progressive development. In CORT-exposed palates, we demonstrate no significant differences in the direction or magnitude of change with time in TGF-beta 1, TGF-beta 3, and EGF-R mRNA levels compared to controls. However, CORT delays by 1 day the down-regulation of palatal TGF-beta 2 transcript normally seen on day 14 of gestation. TGF-beta 2 is known to inhibit cell proliferation. The level of TGF-beta 2 mRNA, the only isoform primarily expressed in the palatal mesenchyme, significantly decreases with progressive palatal development; this down-regulation of TGF-beta 2 expression is associated with increased mesenchymal cell proliferation and palatal shelf growth. CORT, at a critical stage of palatogenesis, induces a delay in the normal down-regulation of TGF-beta 2 gene expression. Given that CORT is known to inhibit mesenchymal cell proliferation and palatal shelf growth, we conclude that the CORT-induced delay in the normal down-regulation of TGF-beta 2 gene expression is probably key event in the pathogenesis of CORT-induced cleft palate.

Embryonic lung maturation in the H-2 congenic pair, B10.A and B10, proceeds at different rates. The dependence of this heterochronic development on maternal haplotype suggests the involvement of a parentally imprinted gene. Since B10.A (H-2a) and B10 (H-2b) mice are genetically identical except for a 3-18 cM region of chromosome 17 that includes the H-2 complex, we sought a promising candidate gene(s) involved in regulating the rate of lung development from genes encoded in this region. The best candidate is the gene encoding the type II insulin-like growth factor receptor (IGF-IIR), whose ligand is the growth factor IGF-II. Only the maternal copy of this gene is expressed in postimplantation embryos. This receptor does not appear to transduce mitogenic signals; instead, IGF-IIR appears to regulate the levels of its ligand available to the growth-promoting type I IGF receptor (IGF-IR). Using in situ hybridization and indirect immunofluorescence, we demonstrate that IGF-IIR mRNA and protein are localized throughout the pulmonary mesenchyme, as well as in branching epithelia of the pseudoglandular and canalicular stages. We also examined the levels of IGF-IIR mRNA and protein expression by RNase protection assay and ligand blotting during the embryonic period of lung development in B10.A and B10 mice, and found that there is a highly significant positive correlation of IGF-IIR levels with progressive development in both strains. Further, slower-developing B10.A lungs contain significantly higher levels of IGF-IIR mRNA and protein than the more rapidly developing B10 lungs. These results suggest that haplotype-dependent elevation of IGF-IIR levels reduces the available concentration of IGF-II, resulting in a decreased rate of morphogenesis in B10.A mice. Heterochronic lung maturation, then, appears consequent to variable extracellular levels of this important growth factor. These results may be of clinical importance to predicting susceptibility to Respiratory Distress Syndrome in prenatal newborns.

In this work, poly(amide-amidic acid) (PAA) was used to modify tetraglycidyl 4,4′-diaminodiphenylmethane (TGDDM)/4,4′-diaminodiphenylsulfone (DDS) system. Results of non-isothermal differential scanning calorimetry analysis indicated that PAA played a role of catalyst during the process of the curing reaction. The curing mechanism was studied by Fourier transform infrared spectroscopy, showing that the PAA acted as a co-curing agent in the system. The glass transition temperature decreased firstly and then increased with the increase of the PAA content. PAA equally rendered TGDDM more fire resistant with higher char yield. On examining the fracture surface morphology using scanning electron microscopy, it was observed that there was no obvious phase separation when the content of PAA was less than 20 phr (per hundred weight of TGDDM/DDS resin), however, phase separation was observed when the content of PAA was 25 and 30 phr. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013