Genome-wide transcriptional analysis of differentially expressed genes in flagellin-pretreated mouse corneal epithelial cells in response to Pseudomonas aeruginosa: involvement of S100A8/A9

We previously showed that pre-exposure of the cornea to Toll-like receptor 5 ligand flagellin induces profound mucosal innate protection against infections by modifying gene expression. Taking advantage of easily procurable epithelial cell population, this study is the first report to use genome-wide cDNA microarray approach to document genes associated with flagellin-induced protection against Pseudomonas aeruginosa in corneal epithelial cells (CECs). Infection altered the expression of 675 genes (497 up and 178 down), while flagellin pretreatment followed by infection resulted in a great increase in 890 gene upregulated and 37 genes downregulated. Comparing these two groups showed 209 differentially expressed genes (157 up, 52 down). Notably, among 114 genes categorized as defense related, S100A8/A9 are the two most highly induced genes by flagellin, and their expression in the corneal was confirmed by realtime PCR and immunohistochemistry. Neutralization of S100A8 and, to a less extent, A9, resulted in significantly increased bacterial burden and severe keratitis. Collectively, our study identifies many differentially expressed genes by flagellin in CECs in response to Pseudomonas. These novel gene expression signatures provide new insights and clues into the nature of protective mechanisms established by flagellin and new therapeutic targets for reducing inflammation and for controlling microbial infection.     

A Sequence Variation: 713-8delC in the Transforming Growth Factor Beta 1 Gene Polymorphism in Thalassemia Major Patients

Osteoporosis remains an important cause of morbidity in β-thalassemia major. Although several factors have been implicated to play an important role in the pathogenesis of osteoporosis and several candidate gene polymorphisms have been found to regulate this process, its pathogenesis has not been completely elucidated. Deletion of a C in the fourth intron sequence 8 base before exon 5 (713-8delC) of transforming growth factor beta 1 (TGF-β1) gene which has been reported significantly higher in the osteoporotic group was studied for its prevalence and association with bone mineral density (BMD) in thalassemia major patients. The aim of this study was to find out the distribution of TGF-β1 (713-8delC) sequence variation and its relationship with BMD in thalassemia major patients. 713-8delC Sequence variation polymorphism was detected in 150 β-thalassemia major patients and their BMD was measured by dual-energy X-ray absorptiometry. Biochemical levels were estimated by enzyme-linked immunosorbent assay. We have found a remarkable incidence (90%) of osteopenia and osteoporosis among regularly transfused patients. We have found no association of 713-8delC variant of TGF-β1 gene with Z-score of BMD at lumbar spine (p = 0.061) and hips (p = 0.773). However, Cc genotype of TGF-β1 gene was found as a risk factor (odds ratio: 3.3) for low bone density in these patients.     

Cigarette smoking duration mediates the association between future thinking and norepinephrine level

Fixating on the present moment rather than considering future consequences of behavior is considered to be a hallmark of drug addiction. As an example, cigarette smokers devalue delayed consequences to a greater extent than nonsmokers, and former smokers devalue delayed consequences more than nonsmokers, but less than current smokers. Further, cigarette smokers have higher norepinephrine levels than nonsmokers, which is indicative of poor future health outcomes. It is unclear how duration of cigarette smoking may impact these associations. The current secondary analysis of publicly available data investigated whether extent of future thinking is associated with smoking duration, as well as norepinephrine level, in a large national US sample (N = 985) of current, former, and never smokers. Individuals scoring lower on future thinking tended to smoke for longer durations and had higher norepinephrine levels relative to individuals scoring higher on future thinking. In addition, duration of cigarette abstinence interacted significantly with future thinking and smoking duration for former smokers. Specifically, the mediation relationship between future thinking, smoking duration, and norepinephrine level for former smokers was strongest at shorter durations of cigarette abstinence and decreased as a function of increasing duration of cigarette abstinence. Overall, results from this study suggest the potential importance of implementing smoking cessation treatments as early as possible for smokers and support future thinking as a potential therapeutic target for smoking cessation treatment.     

Analysis of differentially expressed proteins between HER2 positive and triple negative breast cancer and their prognostic significance

Both triple negative breast cancer (TNBA) and HER2-positive breast cancer lack expression of estrogen receptor alpha (ER) and progesterone receptor (PR), while human epidermal growth factor receptor 2 (HER2) in TNBC is also negative. This study aimed to identify the differentially expressed proteins (DEPs) between TNBC and HER2-positive breast cancer and to improve understanding of their role in the prognosis of breast cancer. By analyzing the breast cancer data set in The Cancer Proteome Atlas (TCPA) database, 15 DEPs between TNBC and HER2-positive breast cancer were identified. GO and pathway enrichment analysis were performed on DEPs, and the protein–protein interaction (PPI) network was constructed. The overall survival (OS) analysis of the breast cancer protein dataset in the Kaplan-Meier plotter showed that low expression of ACC1 suggested a higher OS of HER2-positive breast cancer (HR = 5.34, P < 0.05) and TNBC (HR = 2.88, P < 0.05). And TNBC patients with high TBA1B (HR = 0.16, P < 0.01) or low INPP4B (HR = 3.47, P < 0.05) expression have a better prognosis. Our research provides new insights into the prognostic indicators of TNBC and HER2-positive breast cancer, which could be further studied.     

Review of expandable dental implants

In the last few years the dental implants market has grown both in developed and developing countries, and is associated with high aesthetic expectations and well-being. Although the success rate of commercial implants is high, some problems associated with a lack of initial stability, marginal bony resorption, and periodontal health, remain, especially with immediate placement and loading. The market offers different designs of dental implants, but cylindrical and tapered devices that are fixed to the bone via an external thread are dominant. One lesser-known but potentially useful design is the expandable dental implant (EDI). This paper presents a review of expandable dental implants that encompasses a survey of the literature, published patents, and available commercial devices. We found 15 articles: prospective human trials (n = 4), human case reports (n = 3), published independent discussions of other articles (n = 2), three big animal trials (n = 3), and in silico studies (n = 3). A total of 73 published patents were found and two expandable dental implants are commercially available to date. We propose a classification system that differentiates between the expansion mechanism and the origin of the expanding action. Some expandable designs have been shown to provide good primary stability, but evidence to date is limited. We encourage future clinical and biomechanical studies to clarify and optimise the potential benefits of these implants.     

Fast volumetric imaging of bound and pore water in cortical bone using three‐dimensional ultrashort‐TE (UTE) and inversion recovery UTE sequences

We report the three‐dimensional ultrashort‐TE (3D UTE) and adiabatic inversion recovery UTE (IR‐UTE) sequences employing a radial trajectory with conical view ordering for bi‐component T₂* analysis of bound water (T₂*^BW) and pore water (T₂*^PW) in cortical bone. An interleaved dual‐echo 3D UTE acquisition scheme was developed for fast bi‐component analysis of bound and pore water in cortical bone. A 3D IR‐UTE acquisition scheme employing multiple spokes per IR was developed for bound water imaging. Two‐dimensional UTE (2D UTE) and IR‐UTE sequences were employed for comparison. The sequences were applied to bovine bone samples (n = 6) and volunteers (n = 6) using a 3‐T scanner. Bi‐component fitting of 3D UTE images of bovine samples showed a mean T₂*^BW of 0.26 ± 0.04 ms and T₂*^PW of 4.16 ± 0.35 ms, with fractions of 21.5 ± 3.6% and 78.5 ± 3.6%, respectively. The 3D IR‐UTE signal showed a single‐component decay with a mean T₂*^BW of 0.29 ± 0.05 ms, suggesting selective imaging of bound water. Similar results were achieved with the 2D UTE and IR‐UTE sequences. Bi‐component fitting of 3D UTE images of the tibial midshafts of healthy volunteers showed a mean T₂*^BW of 0.32 ± 0.08 ms and T₂*^PW of 5.78 ± 1.24 ms, with fractions of 34.2 ± 7.4% and 65.8 ± 7.4%, respectively. Single‐component fitting of 3D IR‐UTE images showed a mean T₂*^BW of 0.35 ± 0.09 ms. The 3D UTE and 3D IR‐UTE techniques allow fast volumetric mapping of bound and pore water in cortical bone. Copyright © 2016 John Wiley & Sons, Ltd.     

Promise and limits of the CellSearch platform for evaluating pharmacodynamics in circulating tumor cells

Circulating tumor cells (CTCs), which are captured from blood with anti-epithelial cell adhesion molecule (EpCAM) antibodies, have established prognostic value in specific epithelial cancers, but less is known about their utility for assessing patient response to molecularly targeted agents via measurement of pharmacodynamic (PD) endpoints. We discuss the use of CellSearch (Janssen Diagnostics, LLC, Raritan, NJ) CTC isolation technology for monitoring PD response in early phase trials. We present representative data from three clinical trials with the poly(ADP-ribose) polymerase (PARP) inhibitor veliparib (ABT-888) suggesting that CTCs can be used to measure PD effects. However, while often leading to hypothesis-generating information, our experience points to the difficulty in obtaining sufficient EpCAM-expressing CTCs from patients with advanced disease to reach statistically significant conclusions about PD effects from each trial. Overall, the level of phenotypic heterogeneity observed in specimens from patients with advanced carcinomas suggests caution in the use of cell-surface differentiation marker-based methods for isolating CTCs.