51 research outputs found

    Urinary Malondialdehyde Is Associated with Visceral Abdominal Obesity in Middle-Aged Men

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    The purpose of the present study was to investigate multiple anthropometric parameters used to evaluate obesity, particularly visceral abdominal fat area, and various metabolic parameters including malondialdehyde (MDA) as an oxidative stress marker. We evaluated various measures of obesity, including body mass index (BMI), waist circumference (WC), sagittal abdominal diameter, fat percentages using dual-energy X-ray absorptiometry, visceral fat area (VFA), subcutaneous fat area, multiple biomarkers related to metabolic disease, and urinary MDA, in 73 asymptomatic middle-aged men who were not severely obese. We examined relationships between multiple measures of obesity, metabolic markers, and urinary MDA levels and evaluated associations between VFA and urinary MDA. In the visceral obesity group, -glutamyl transferase (GGT), uric acid, and urinary MDA levels were significantly higher than in the nonvisceral obesity group (P = 0.008, P = 0.002, and P = 0.018). Urinary MDA (r = 0.357, P = 0.002) and uric acid (r = 0.263, P = 0.027) levels were only significantly positively correlated with VFA among measures of obesity. Urinary MDA, serum GGT, and serum CRP were significantly positively associated with VFA (P = 0.001, P = 0.046, and P = 0.023, resp.), even after adjusting for BMI and WC

    Cancer-Associated Splicing Variant of Tumor Suppressor AIMP2/p38: Pathological Implication in Tumorigenesis

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    Although ARS-interacting multifunctional protein 2 (AIMP2, also named as MSC p38) was first found as a component for a macromolecular tRNA synthetase complex, it was recently discovered to dissociate from the complex and work as a potent tumor suppressor. Upon DNA damage, AIMP2 promotes apoptosis through the protective interaction with p53. However, it was not demonstrated whether AIMP2 was indeed pathologically linked to human cancer. In this work, we found that a splicing variant of AIMP2 lacking exon 2 (AIMP2-DX2) is highly expressed by alternative splicing in human lung cancer cells and patient's tissues. AIMP2-DX2 compromised pro-apoptotic activity of normal AIMP2 through the competitive binding to p53. The cells with higher level of AIMP2-DX2 showed higher propensity to form anchorage-independent colonies and increased resistance to cell death. Mice constitutively expressing this variant showed increased susceptibility to carcinogen-induced lung tumorigenesis. The expression ratio of AIMP2-DX2 to normal AIMP2 was increased according to lung cancer stage and showed a positive correlation with the survival of patients. Thus, this work identified an oncogenic splicing variant of a tumor suppressor, AIMP2/p38, and suggests its potential for anti-cancer target

    Radiogenomics Profiling for Glioblastoma-related Immune Cells Reveals CD49d Expression Correlation with MRI parameters and Prognosis

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    Although there have been a plethora of radiogenomics studies related to glioblastoma (GBM), most of them only used genomic information from tumor cells. In this study, we used radiogenomics profiling to identify MRI-associated immune cell markers in GBM, which was also correlated with prognosis. Expression levels of immune cell markers were correlated with quantitative MRI parameters in a total of 60 GBM patients. Fourteen immune cell markers (i.e., CD11b, CD68, CSF1R, CD163, CD33, CD123, CD83, CD63, CD49d and CD117 for myeloid cells, and CD4, CD3e, CD25 and CD8 for lymphoid cells) were selected for RNA-level analysis using quantitative RT-PCR. For MRI analysis, quantitative MRI parameters from FLAIR, contrast-enhanced (CE) T1WI, dynamic susceptibility contrast perfusion MRI and diffusion-weighted images were used. In addition, PFS associated with interesting mRNA data was performed by Kaplan-Meier survival analysis. CD163, which marks tumor associated microglia/macrophages (TAMs), showed the highest expression level in GBM patients. CD68 (TAMs), CSF1R (TAMs), CD33 (myeloid-derived suppressor cell) and CD4 (helper T cell, regulatory T cell) levels were highly positively correlated with nCBV values, while CD3e (helper T cell, cytotoxic T cell) and CD49d showed a significantly negative correlation with apparent diffusion coefficient (ADC) values. Moreover, regardless of any other molecular characteristics, CD49d was revealed as one independent factor for PFS of GBM patients by Cox proportional-hazards regression analysis (P = 0.0002). CD49d expression level CD49d correlated with ADC can be considered as a candidate biomarker to predict progression of GBM patients. © The Author(s) 201

    Accessing power-law statistics under experimental constraints

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    Power-law distributions appear in a large variety of situations and influence our understanding of various physical phenomena. Their identification and characterization are notoriously difficult because of the large fluctuations inherent to empirical data and also because of the unknown range over which the power-law behavior holds. Furthermore, the data on which one is trying to detect power laws are affected by technical constraints and experimental limitations. Here, we show how a power-law distribution is modified by two fundamental limitations: the spatiotemporal resolution and the time window. We consider a time series of events or states and investigate the interevent time probability density function (PDF) or the PDF of the duration of a state. We present in detail how each limitation affects the PDF and derive mathematical expressions that relate the observed distribution to the true one: the resolution globally affects the shape of PDF while preserving the asymptotic exponent and the time window introduces a nonexponential cutoff. We demonstrate that, instead of looking for a simple power law in experimental data, one should fit the data with the modified PDF that we derived for given experimental constraints. We apply our theory to data from an experimental study of the transport of mRNA-protein complexes along dendrites. The presented mathematical theory widens our understanding of the identification and characterization of power-law distributions in experimental data and can be used in a broad spectrum of science fields.11Yscopu

    BCAT1 is a New MR Imaging-related Biomarker for Prognosis Prediction in IDH1-wildtype Glioblastoma Patients

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    Isocitrate dehydrogenase 1 (IDH1)-wildtype glioblastoma (GBM) has found to be accompanied with increased expression of branched-chain amino acid trasaminase1 (BCAT1), which is associated with tumor growth and disease progression. In this retrospective study, quantitative RT-PCR, immunohistochemistry, and western blot were performed with GBM patient tissues to evaluate the BCAT1 level. Quantitative MR imaging parameters were evaluated from DSC perfusion imaging, DWI, contrast-enhanced T1WI and FLAIR imaging using a 3T MR scanner. The level of BCAT1 was significantly higher in IDH1-wildtype patients than in IDH1-mutant patients obtained in immunohistochemistry and western blot. The BCAT1 level was significantly correlated with the mean and 95th percentile-normalized CBV as well as the mean ADC based on FLAIR images. In addition, the 95th percentile-normalized CBV from CE T1WI also had a significant correlation with the BCAT1 level. Moreover, the median PFS in patients with BCAT1 expression <100 was longer than in those with BCAT1 expression ≥100. Taken together, we found that a high BCAT1 level is correlated with high CBV and a low ADC value as well as the poor prognosis of BCAT1 expression is related to the aggressive nature of GBM. © 2017 The Author(s)
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