Identification of Gene Expression Signature Modulated by Nicotinamide in a Mouse Bladder Cancer Model

BACKGROUND: Urinary bladder cancer is often a result of exposure to chemical carcinogens such as cigarette smoking. Because of histological similarity, chemically-induced rodent cancer model was largely used for human bladder cancer studies. Previous investigations have suggested that nicotinamide, water-soluble vitamin B3, may play a key role in cancer prevention through its activities in cellular repair. However, to date, evidence towards identifying the genetic alterations of nicotinamide in cancer prevention has not been provided. Here, we search for the molecular signatures of cancer prevention by nicotinamide using a N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced urinary bladder cancer model in mice. METHODOLOGY/PRINCIPAL FINDINGS: Via microarray gene expression profiling of 20 mice and 233 human bladder samples, we performed various statistical analyses and immunohistochemical staining for validation. The expression patterns of 893 genes associated with nicotinamide activity in cancer prevention were identified by microarray data analysis. Gene network analyses of these 893 genes revealed that the Myc and its associated genes may be the most important regulator of bladder cancer prevention, and the gene expression signature correlated well with protein expression data. Comparison of gene expression between human and mouse revealed that BBN-induced mouse bladder cancers exhibited gene expression profiles that were more similar to those of invasive human bladder cancers than to those of non-invasive human bladder cancers. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that nicotinamide plays an important role as a chemo-preventive and therapeutic agent in bladder cancer through the regulation of the Myc oncogenic signature. Nicotinamide may represent a promising therapeutic modality in patients with muscle-invasive bladder cancer

The Antiviral Effect of High-Molecular Weight Poly-Gamma-Glutamate against Newcastle Disease Virus on Murine Macrophage Cells

This study demonstrates the capacity of HM-γ-PGA treatment to significantly protect murine macrophage cells (RAW 264.7 cells) against NDV infection. Such protection can be explained by the induction of antiviral state of HM-γ-PGA in RAW 264.7 cells via TLR4-mediated IRF-3, IRF-7, IFN-β, and IFN-related gene induction as shown in time-dependent changes in mRNA expression confirmed by polymerase chain reaction (PCR). Moreover, the present research also showed that HM-γ-PGA can induce proinflammatory cytokine secretion in RAW 264.7 as measured by enzyme-linked immunosorbent assay (ELISA). Therefore, our findings suggest that HM-γ-PGA can be a potential antiviral substance that can inhibit NDV infection through its stimulation of antiviral state on RAW 264.7 cells. These results have been consistent with the previous studies showing that HM-γ-PGA can protect RAW 264.7 cells and mice against influenza infection. However, it should be noted that although murine macrophage cells are susceptible to NDV, they are not the natural host cells of the virus; thus further in vivo and in vitro studies involving chicken and chicken immune cells are needed to fully assess the efficacy and applicability of HM-γ-PGA in the poultry industry

Optimization of magnetic flux density for fast MREIT conductivity imaging using multi-echo interleaved partial fourier acquisitions

BACKGROUND: Magnetic resonance electrical impedance tomography (MREIT) has been introduced as a non-invasive method for visualizing the internal conductivity and/or current density of an electrically conductive object by externally injected currents. The injected current through a pair of surface electrodes induces a magnetic flux density distribution inside the imaging object, which results in additional magnetic flux density. To measure the magnetic flux density signal in MREIT, the phase difference approach in an interleaved encoding scheme cancels out the systematic artifacts accumulated in phase signals and also reduces the random noise effect by doubling the measured magnetic flux density signal. For practical applications of in vivo MREIT, it is essential to reduce the scan duration maintaining spatial-resolution and sufficient contrast. In this paper, we optimize the magnetic flux density by using a fast gradient multi-echo MR pulse sequence. To recover the one component of magnetic flux density B(z), we use a coupled partial Fourier acquisitions in the interleaved sense. METHODS: To prove the proposed algorithm, we performed numerical simulations using a two-dimensional finite-element model. For a real experiment, we designed a phantom filled with a calibrated saline solution and located a rubber balloon inside the phantom. The rubber balloon was inflated by injecting the same saline solution during the MREIT imaging. We used the multi-echo fast low angle shot (FLASH) MR pulse sequence for MRI scan, which allows the reduction of measuring time without a substantial loss in image quality. RESULTS: Under the assumption of a priori phase artifact map from a reference scan, we rigorously investigated the convergence ratio of the proposed method, which was closely related with the number of measured phase encode set and the frequency range of the background field inhomogeneity. In the phantom experiment with a partial Fourier acquisition, the total scan time was less than 6 seconds to measure the magnetic flux density B(z) data with 128×128 spacial matrix size, where it required 10.24 seconds to fill the complete k-space region. CONCLUSION: Numerical simulation and experimental results demonstrated that the proposed method reduces the scanning time and provides the recovered B(z) data comparable to what we obtained by measuring complete k-space data

The Impact of International Migration on Unemployment Rates in Urban America: Testing Different Theoretical Approaches

This study examines the influence of international migration on unemployment rates in urban America. For this purpose, this study first applies competition and discrimination and assimilation views in examining whether the size and composition of immigrant populations in American metropolitan areas affect urban unemployment rates. Based on local human capital and labor market views, this study also explores whether urban unemployment rates are affected by local human capital (education) and urban labor markets (employment distributions by class of workers), both of which vary with the size and compositions of local immigrant populations. Using a sample of the 301 Primary Metropolitan Statistical Areas /Metropolitan Statistical Areas (PMSAs/MSAs) in 1990 and 2000, this study employs regression models to test four hypotheses. First, the result supports to some degree competition and discrimination and assimilation views. The empirical findings show that more concentration of international migrants in urban areas, including recent immigrant cohorts, tends to increase urban unemployment rates. Second, the models of local human capital also support that growing college graduates play a role in reducing urban unemployment rates after controlling for the volume of immigrant population. However, there are conflicting impacts of local labor market (employment conditions) on urban unemployment rates

Impact of Neuroimaging Patterns for the Detection of Atrial Fibrillation by Implantable Loop Recorders in Patients With Embolic Stroke of Undetermined Source

ObjectivesAtrial fibrillation (AF) is a well-known etiology of embolic stroke of undetermined source (ESUS), although the optimal detection strategy of AF was not been fully evaluated yet. We assessed AF detection rate by implantable loop recorder (ILR) in patients with ESUS and compared the clinical characteristics and neuroimaging patterns between the patients with AF and AF-free patients.MethodsWe reviewed clinical characteristics and neuroimaging patterns of consecutive patients with who were admitted to our comprehensive stroke center for ESUS and underwent ILR insertion between August 1, 2019, and January 31, 202. The inclusion criteria were (1) 18 years of age or older; (2) classified as having cryptogenic stroke extracted from the group with undetermined stroke according to ESUS International Working Group; and (3) underwent ILR insertion during or after admission due to index ischemic events. Ischemic stroke pattern was classified as (1) tiny-scattered infarction, (2) whole-territorial infarction, (3) lobar infarction and (4) multiple-territorial infarction. Interrogations of data retrieved from the ILR were performed by cardiologists in every month after the implantation.ResultsIn this study, 41 ESUS patients who received an ILR implantation were enrolled (mean age, 64 years; male sex, 65.9%). The rate of AF detection at 6 months was 34% (14 patients), and the mean time from ILR insertion to AF detection was 52.5 days [interquartile range (IQR), 45.0–69.5]. The median initial NIH stroke scale scores were significantly greater in patients with AF than those without AF (6.5 vs. 3.0, p = 0.019). Whole-territorial infarction pattern was significantly more frequent in patients with AF than in those without AF (64.3% vs.11.1%, p = 0.002).ConclusionsHigher covert AF detection rates within the ESUS patients were most often associated with higher NIHSS and whole-territorial infarction patterns on brain imaging