Transgelin gene is frequently downregulated by promoter DNA hypermethylation in breast cancer

Tables not included in the main manuscript have been listed. Table S1. Number of probe sets affected by AZA treatment; Table S2. Comparison of significantly altered probe sets with the independent study GSE20713 Dataset; Table S3. Cancer vs. normal analysis of TAGLN mRNA in Oncomine database. (PDF 18 kb

Diagnostic performance and interobserver agreement of CO-RADS: evaluation of classification in radiology practice

PURPOSEWe aimed to evaluate the use of the COVID-19 reporting and data system (CO-RADS) among radiologists and the diagnostic performance of this system.METHODSFour radiologists retrospectively evaluated the chest CT examinations of 178 patients. The study included 143 patients with positive reverse transcriptase-polymerase chain reaction (RT-PCR) test results and 35 patients whose RT-PCR tests were negative but whose clinical and/or radiological findings were consistent with COVID-19. Fleiss’ kappa (κ) values were calculated, and individual observers’ scores were compared. To investigate diagnostic efficiency, receiver operating characteristic (ROC) curves were calculated for each interpreter.RESULTSThe interpreters were in full agreement on 574 of 712 (80.6%) evaluations. The common Fleiss’ κ value of all the radiologists combined was 0.712 (95% confidence interval [CI] 0.692–0.769). A reliable prediction on the basis of RT-PCR and clinical findings indicated the mean area under the curve (AUC) of Fleiss’ κ value as 0.89 (95% CI 0.708–0.990). General interpreter agreement was found to range from moderate to good.CONCLUSIONThe interpreter agreement for CO-RADS categories 1 and 5 was reasonably good. We conclude that this scoring system will make a valuable contribution to efforts in COVID-19 diagnosis. CO-RADS can also be of significant value for the diagnosis and treatment of the disease in cases with false-negative PCR results

Vitiligo in a Patient Treated with Interferon Alpha-2a for Behçet’s Disease

Behçet’s disease (BD) and vitiligo are diseases of unknown etiology. Interferon (IFN) alpha therapy is commonly used in Behçet uveitis. Interferon treatment in various diseases have also been observed causing certain autoimmune diseases such as vitiligo because of its immunomodulatory activity. The association between IFN therapy and vitiligo has been reported in the literature. We report a 21-year-old man with BD in whom vitiligo occurred during IFN treatment. To the best of our knowledge, this is the first reported case of such an association

Diet-associated inflammation modulates inflammation and WNT signaling in the rectal mucosa, and the response to supplementation with dietary fiber

Inflammation drives colorectal cancer development, and colorectal cancer risk is influenced by dietary factors, including dietary fiber. Hyperactive WNT signaling occurs in colorectal cancer and may regulate inflammation. This study investigated (i) relationships between the inflammatory potential of diet, assessed using the Energy-adjusted Dietary Inflammatory Index (E-DII), and markers of WNT signaling, and (ii) whether DII status modulated the response to supplementation with two types of dietary fiber. Seventy-five healthy participants were supplemented with resistant starch and/or polydextrose (PD) or placebo for 50 days. Rectal biopsies were collected before and after intervention and used to assess WNT pathway gene expression and crypt cell proliferation. E-DII scores were calculated from food frequency questionnaire data. High-sensitivity C-reactive protein (hsCRP) and fecal calprotectin concentrations were quantified. hsCRP concentration was significantly greater in participants with higher E-DII scores [least square means (LSM) 4.7 vs. 2.4 mg/L, P = 0.03]. Baseline E-DII score correlated with FOSL1 (b = 0.503, P = 0.003) and WNT11 (b = 0.472, P = 0.006) expression, after adjusting for age, gender, body mass index, endoscopy procedure, and smoking status. WNT11 expression was more than 2-fold greater in individuals with higher E-DII scores (LSM 0.131 vs. 0.059, P = 0.002). Baseline E-DII modulated the effects of PD supplementation on FOSL1 expression (P = 0.04). More proinflammatory diets were associated with altered WNT signaling and appeared to modulate the effects of PD supplementation on expression of FOSL1. This is the first study to investigate relationships between the E-DII and molecular markers of WNT signaling in rectal tissue of healthy individuals

The Ability to Generate Senescent Progeny as a Mechanism Underlying Breast Cancer Cell Heterogeneity

Background Breast cancer is a remarkably heterogeneous disease. Luminal, basal-like, "normal-like", and ERBB2+ subgroups were identified and were shown to have different prognoses. The mechanisms underlying this heterogeneity are poorly understood. In our study, we explored the role of cellular differentiation and senescence as a potential cause of heterogeneity. Methodology/Principal Findings A panel of breast cancer cell lines, isogenic clones, and breast tumors were used. Based on their ability to generate senescent progeny under low-density clonogenic conditions, we classified breast cancer cell lines as senescent cell progenitor (SCP) and immortal cell progenitor (ICP) subtypes. All SCP cell lines expressed estrogen receptor (ER). Loss of ER expression combined with the accumulation of p21Cip1 correlated with senescence in these cell lines. p21Cip1 knockdown, estrogen-mediated ER activation or ectopic ER overexpression protected cells against senescence. In contrast, tamoxifen triggered a robust senescence response. As ER expression has been linked to luminal differentiation, we compared the differentiation status of SCP and ICP cell lines using stem/progenitor, luminal, and myoepithelial markers. The SCP cells produced CD24+ or ER+ luminal-like and ASMA+ myoepithelial-like progeny, in addition to CD44+ stem/progenitor-like cells. In contrast, ICP cell lines acted as differentiation-defective stem/progenitor cells. Some ICP cell lines generated only CD44+/CD24-/ER-/ASMA- progenitor/stem-like cells, and others also produced CD24+/ER- luminal-like, but not ASMA+ myoepithelial-like cells. Furthermore, gene expression profiles clustered SCP cell lines with luminal A and "normal-like" tumors, and ICP cell lines with luminal B and basal-like tumors. The ICP cells displayed higher tumorigenicity in immunodeficient mice. Conclusions/Significance Luminal A and "normal-like" breast cancer cell lines were able to generate luminal-like and myoepithelial-like progeny undergoing senescence arrest. In contrast, luminal B/basal-like cell lines acted as stem/progenitor cells with defective differentiation capacities. Our findings suggest that the malignancy of breast tumors is directly correlated with stem/progenitor phenotypes and poor differentiation potential. © 2010 Mumcuoglu et al

A resampling-based meta-analysis for detection of differential gene expression in breast cancer

<p>Abstract</p> <p>Background</p> <p>Accuracy in the diagnosis of breast cancer and classification of cancer subtypes has improved over the years with the development of well-established immunohistopathological criteria. More recently, diagnostic gene-sets at the mRNA expression level have been tested as better predictors of disease state. However, breast cancer is heterogeneous in nature; thus extraction of differentially expressed gene-sets that stably distinguish normal tissue from various pathologies poses challenges. Meta-analysis of high-throughput expression data using a collection of statistical methodologies leads to the identification of robust tumor gene expression signatures.</p> <p>Methods</p> <p>A resampling-based meta-analysis strategy, which involves the use of resampling and application of distribution statistics in combination to assess the degree of significance in differential expression between sample classes, was developed. Two independent microarray datasets that contain normal breast, invasive ductal carcinoma (IDC), and invasive lobular carcinoma (ILC) samples were used for the meta-analysis. Expression of the genes, selected from the gene list for classification of normal breast samples and breast tumors encompassing both the ILC and IDC subtypes were tested on 10 independent primary IDC samples and matched non-tumor controls by real-time qRT-PCR. Other existing breast cancer microarray datasets were used in support of the resampling-based meta-analysis.</p> <p>Results</p> <p>The two independent microarray studies were found to be comparable, although differing in their experimental methodologies (Pearson correlation coefficient, R = 0.9389 and R = 0.8465 for ductal and lobular samples, respectively). The resampling-based meta-analysis has led to the identification of a highly stable set of genes for classification of normal breast samples and breast tumors encompassing both the ILC and IDC subtypes. The expression results of the selected genes obtained through real-time qRT-PCR supported the meta-analysis results.</p> <p>Conclusion</p> <p>The proposed meta-analysis approach has the ability to detect a set of differentially expressed genes with the least amount of within-group variability, thus providing highly stable gene lists for class prediction. Increased statistical power and stringent filtering criteria used in the present study also make identification of novel candidate genes possible and may provide further insight to improve our understanding of breast cancer development.</p

Plant Toxic Proteins: Their Biological Activities, Mechanism of Action and Removal Strategies

Plants evolve to synthesize various natural metabolites to protect themselves against threats, such as insects, predators, microorganisms, and environmental conditions (such as temperature, pH, humidity, salt, and drought). Plant-derived toxic proteins are often secondary metabolites generated by plants. These proteins, including ribosome-inactivating proteins, lectins, protease inhibitors, α-amylase inhibitors, canatoxin-like proteins and ureases, arcelins, antimicrobial peptides, and pore-forming toxins, are found in different plant parts, such as the roots, tubers, stems, fruits, buds, and foliage. Several investigations have been conducted to explore the potential applications of these plant proteins by analyzing their toxic effects and modes of action. In biomedical applications, such as crop protection, drug development, cancer therapy, and genetic engineering, toxic plant proteins have been utilized as potentially useful instruments due to their biological activities. However, these noxious metabolites can be detrimental to human health and cause problems when consumed in high amounts. This review focuses on different plant toxic proteins, their biological activities, and their mechanisms of action. Furthermore, possible usage and removal strategies for these proteins are discussed

Comparison of diagnostic value of multidetector computed tomography and X-ray in the detection of body packing

Objective: Radiologists and other clinicians are facing an increasing number of illegal drug-related medical conditions. We aimed to draw attention to this growing global problem and to highlight some of the important points related to diagnosis and follow-up of body packing. We compare the diagnostic performance of unenhanced multidetector CT (MDCT) and abdomen X-ray for the detection of drug-filled packets

Association between dental caries and adherence to the Mediterranean diet, dietary intake, and body mass index in children

Abstract Background Children with healthier nutritional status are less likely to develop severe caries than those with a high-sugar content diet. Studies evaluating dental caries and nutritional status in school-age children have generally focused on dietary intake, diet quality, or anthropometric measures, and the number of studies evaluating them together is limited. Objective It was aimed to evaluate the relationship between dental caries adherence to the Mediterranean Diet (MD), dietary intake, and Body Mass Index (BMI) in school-age children. Materials and methods This study was conducted with 300 healthy children (52.0% boys, 48.0% girls) aged between 6 and 12 years. The data collection forms included sociodemographic characteristics, oral health practices of children, Mediterranean Diet Quality Index for children and adolescents (KIDMED), and food consumption records. Anthropometric measurements (body weight and height) of the children were taken. Dental examinations were performed by a pediatric dentist. Results While the DMFT mean score of the children was 1.7 ± 2.09, the mean dft score was 2.9 ± 3.29. The mean of KIDMED scores was 5.9 ± 3.32. DMFT and dft scores decreased statistically as maternal education increased (p  0.05). DMFT scores differed statistically between KIDMED groups (p < 0.05). This difference was between low-optimal and low-improvement-needed groups. While there was a low negative correlation (r=-0.169) between calcium intake and DMFT score, a low positive correlation was found between glucose (r = 0.172) and fructose (r = 0.149) intake and dft score (p < 0.05). In regression analysis, while the children’s age related DMFT scores positively, maternal education and KIDMED scores related DMFT scores negatively. Also, children’s age and maternal education related dft scores negatively. Conclusion In this study, adherence to the MD rather than nutrients was found to be important in dental caries. Also maternal education level was also found to be a determinant factor in dental caries in children. DMFT and dft did not differ between BMI groups.Further studies should be conducted to assess the impact of the MD on dental caries in children to develop dietary interventions for preventative purposes

Superparamagnetic Iron Oxide-Enhanced Magnetic Resonance Imaging in a Case of Spleen Hamartoma

Objective: To emphasize the contribution of superparamagnetic iron oxide (SPIO) contrast agent in the diagnosis of the splenic hamartoma. Clinical Presentation and Intervention: A 63-year-old female was admitted to our hospital with diffuse abdominal pain. An ultrasound examination revealed a 5 x 4 cm solid lesion in the spleen. Dynamic gadolinium-enhanced magnetic resonance imaging (MRI) of the abdominal findings was consistent with a splenic hamartoma. SPIO-enhanced MRI was then performed and it confirmed the diagnosis. The lesion showed a decrease of signal intensity on T2-weighted images. Conclusion: This case showed that SPIO-enhanced MRI was useful for establishing a noninvasive diagnosis of the splenic hamartomas. Copyright (C) 2012 S. Karger AG, Base