Interplay between 15-lipoxygenase-1 and metastasis-associated antigen 1 in the metastatic potential of colorectal cancer

Objectives: Metastasis-associated antigen 1 (MTA1) is implicated in metastasis while 15-lipoxygenase-1 (15-LOX-1) reduces cell motility, when re-expressed in colorectal cancer (CRC). We aimed to understand any potential interplay between MTA1 and 15-LOX-1 in CRC metastasis. Materials and methods: ALOX15 and MTA1 expression in tumour and normal samples were analysed from TCGA RNA-seq data, microarray data sets and a human CRC cDNA array. Western blots, chromatin immunoprecipitation (ChIP), luciferase assays and electrophoretic mobility shift assays (EMSA) were carried out in HT-29 and LoVo cells re-expressing 15-LOX-1 to determine NF- κB activity at the MTA1 promoter. Functional assays in cells ectopically expressing either 15-LOX-1, MTA-1 or both, were carried out to determine adhesion and cell motility. Results: Significantly higher expression of MTA1 was observed in tumours compared to normal tissues; MTA1 overexpression resulted in reduced adhesion in CRC cell lines. Re-expression of 15-LOX-1 in the CRC cell lines reduced expression of endogenous MTA1, corroborated by negative correlation between the two genes in two independent human CRC microarray data sets, with greater significance in specific subsets of patients. DNA binding and transcriptional activity of NF-κB at the MTA1 promoter was significantly lower in cells re-expressing 15-LOX-1. Functionally, the same cells had reduced motility, which was rescued when they overexpressed MTA1, and further corroborated by expressions of E-cadherin and vimentin. Conclusions: Expression of MTA1 and 15-LOX-1 negatively correlated in specific subsets of CRC. Mechanistically, this is at least in part through reduced recruitment of NF-κB to the MTA1 promoter. © 2016 John Wiley & Sons Lt

15-Lipoxygenase-1 re-expression in colorectal cancer alters endothelial cell features through enhanced expression of TSP-1 and ICAM-1

15-lipoxygenase-1 (15-LOX-1) oxygenates linoleic acid to 13(S)-hydroxyoctadecadienoic acid (HODE). The enzyme is widely suppressed in different cancers and its re-expression has tumor suppressive effects. 15-LOX-1 has been shown to inhibit neoangiogenesis in colorectal cancer (CRC); in the present study we confirm this phenomenon and describe the mechanistic basis. We show that re-expression of 15-LOX-1 in CRC cell lines resulted in decreased transcriptional activity of HIF1α and reduced the expression and secretion of VEGF in both normoxic and hypoxic conditions. Conditioned medium (CM) was obtained from CRC or prostate cancer cell lines re-expressing 15-LOX-1 (15-LOX-1CM). 15-LOX-1CM treated aortic rings from 6-week old C57BL/6 mice showed significantly less vessel sprouting and more organized structure of vascular network. Human umbilical vein endothelial cells (HUVECs) incubated with 15-LOX-1CM showed reduced motility, enhanced expression of intercellular cell adhesion molecule (ICAM-1) and reduced tube formation but no change in proliferation or cell-cycle distribution. HUVECs incubated with 13(S)-HODE partially phenocopied the effects of 15-LOX-1CM, i.e., showed reduced motility and enhanced expression of ICAM-1, but did not reduce tube formation, implying the importance of additional factors. Therefore, a Proteome Profiler Angiogenesis Array was carried out, which showed that Thrombospondin-1 (TSP-1), a matrix glycoprotein known to strongly inhibit neovascularization, was expressed significantly more in HUVECs incubated with 15-LOX-1CM. TSP-1 blockage in HUVECs reduced the expression of ICAM-1 and enhanced cell motility, thereby providing a mechanism for reduced angiogenesis. The anti-angiogenic effects of 15-LOX-1 through enhanced expressions of ICAM-1 and TSP-1 are novel findings and should be explored further to develop therapeutic options. © 201

The frequency of microscopic and focal active colitis in patients with irritable bowel syndrome

<p>Abstract</p> <p>Background</p> <p>Irritable bowel syndrome (IBS) is a chronic functional bowel disorder. The frequency of microscopic colitis and focal active colitis in the colonic mucosa has been investigated in IBS patients.</p> <p>Methods</p> <p>Between June 2007 and September 2010, 378 patients (between 16 and 84 years) were recruited prospectively. Of these 378 patients, 226 patients were diagnosed with IBS using the Rome III criteria. 152 control patients were also enrolled who were undergoing colonoscopy for colorectal cancer screening or investigation of anemia. Histopathological abnormalities identified during colonoscopy were compared between the IBS and control groups.</p> <p>Results</p> <p>The average age of the IBS group was 46.13 ± 14.16 years and and the average age of the control group was 57.01 ± 13.07 years. The prevalence of microscopic colitis (MC) in the diarrhea predominant and the mixed subgroup of IBS patients was 4.32% (7/162) whereas in all IBS patients, the prevalence was 3.09% (7/226). MC was not found in the 152 control cases, (p = 0.045). Lymphocytic colitis was seen in 7 IBS patients, with 1 case in the mixed group and 6 cases in the diarrhea group and there was a significant difference in the frequency of lymphocytic colitis between the IBS subgroups (p < 0.01). Focal active colitis was found in 6.6% (15/226) of the IBS patients and in none of the controls (p < 0.01), and there was no differences between IBS subtypes.</p> <p>Conclusion</p> <p>Microscopic colitis was more often found in the diarrhea predominant/mixed subgroups of IBS patients and in patients who were older women. In patients who are older woman with non-constipated IBS, it may be reasonable to perform a biopsy to screen for microscopic colitis. Focal active colitis was significantly increased in patients with IBS compared to controls.</p

Role of anatomical sites and correlated risk factors on the survival of orthodontic miniscrew implants:a systematic review and meta-analysis

Abstract Objectives The aim of this review was to systematically evaluate the failure rates of miniscrews related to their specific insertion site and explore the insertion site dependent risk factors contributing to their failure. Search methods An electronic search was conducted in the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Knowledge, Scopus, MEDLINE and PubMed up to October 2017. A comprehensive manual search was also performed. Eligibility criteria Randomised clinical trials and prospective non-randomised studies, reporting a minimum of 20 inserted miniscrews in a specific insertion site and reporting the miniscrews’ failure rate in that insertion site, were included. Data collection and analysis Study selection, data extraction and quality assessment were performed independently by two reviewers. Studies were sub-grouped according to the insertion site, and the failure rates for every individual insertion site were analysed using a random-effects model with corresponding 95% confidence interval. Sensitivity analyses were performed in order to test the robustness of the reported results. Results Overall, 61 studies were included in the quantitative synthesis. Palatal sites had failure rates of 1.3% (95% CI 0.3–6), 4.8% (95% CI 1.6–13.4) and 5.5% (95% CI 2.8–10.7) for the midpalatal, paramedian and parapalatal insertion sites, respectively. The failure rates for the maxillary buccal sites were 9.2% (95% CI 7.4–11.4), 9.7% (95% CI 5.1–17.6) and 16.4% (95% CI 4.9–42.5) for the interradicular miniscrews inserted between maxillary first molars and second premolars and between maxillary canines and lateral incisors, and those inserted in the zygomatic buttress respectively. The failure rates for the mandibular buccal insertion sites were 13.5% (95% CI 7.3–23.6) and 9.9% (95% CI 4.9–19.1) for the interradicular miniscrews inserted between mandibular first molars and second premolars and between mandibular canines and first premolars, respectively. The risk of failure increased when the miniscrews contacted the roots, with a risk ratio of 8.7 (95% CI 5.1–14.7). Conclusions Orthodontic miniscrew implants provide acceptable success rates that vary among the explored insertion sites. Very low to low quality of evidence suggests that miniscrews inserted in midpalatal locations have a failure rate of 1.3% and those inserted in the zygomatic buttress have a failure rate of 16.4%. Moderate quality of evidence indicates that root contact significantly contributes to the failure of interradicular miniscrews placed between the first molars and second premolars. Results should be interpreted with caution due to methodological drawbacks in some of the included studies

Imageability ratings across languages

Imageability is a psycholinguistic variable that indicates how well a word gives rise to a mental image or sensory experience. Imageability ratings are used extensively in psycholinguistic, neuropsychological, and aphasiological studies. However, little formal knowledge exists about whether and how these ratings are associated between and within languages. Fifteen imageability databases were cross-correlated using nonparametric statistics. Some of these corresponded to unpublished data collected within a European research network-the Collaboration of Aphasia Trialists (COST IS1208). All but four of the correlations were significant. The average strength of the correlations (rho = .68) and the variance explained (R (2) = 46%) were moderate. This implies that factors other than imageability may explain 54% of the results. Imageability ratings often correlate across languages. Different possibly interacting factors may explain the moderate strength and variance explained in the correlations: (1) linguistic and cultural factors; (2) intrinsic differences between the databases; (3) range effects; (4) small numbers of words in each database, equivalent words, and participants; and (5) mean age of the participants. The results suggest that imageability ratings may be used cross-linguistically. However, further understanding of the factors explaining the variance in the correlations will be needed before research and practical recommendations can be made

Development of drying model and determination of color characteristics for combined microwave-fan assisted convection drying of green tea

The effects of microwave drying (180, 360, 540, 720 and 900 W); combined convective (100, 180, 230 °C) and microwave drying (180 and 540 W); and convective drying (100, 180, 230 °C) on drying time, drying rate and change in color of green tea (Camellia sinensis L.) leaves were investigated. Eleven different thin layer mathematical drying models were compared based on their coefficient of determination (R 2), standard error of estimate (SEE) and residual sum of squares (RSS) to estimate the drying curves. The Midilli-Kucuk model described the drying curve best in all drying methods (R 2 = 0.9988-1.0000, SEE = 0.0024-0.0201, RSS = 0.0001-0.0054). The results closest to fresh sample values with respect to color criteria were obtained from microwave drying followed by microwave-convective drying and convective drying

A heuristic approach to minimising maximum lateness on a single machine

This paper focuses on the problem of scheduling on a single machine to minimise the maximum lateness when each job has a different ready time, processing time, and due date. A simple procedure is developed to find a better solution than the early due date (EDD) algorithm. The new algorithm suggested in this paper is called Least Slack Time - Look Ahead (LST-LA), which minimises the maximum lateness problem. Computational results show that when the number of jobs increases, LST-LA outperforms EDD

Facilitating the complexity of architectural analyses

It is common practice for architecture students to collect documents on prominent buildings relevant to their design task in the early stage of design. While practitioners can rely on a body of design experience of their own, during the process of a new design, students can only draw from the examples of success and failure from other architects. In the past, such precedent based learning was implicit in the master-apprentice relationship common in the educational system. Nowadays academics commonly no longer have the possibility to maintain an extensive design practice, and instead introduce important outside precedents to the students. Thus, the study of important historical precedents or designs plays an important role in design instruction and in the studentsi design processes. While there is no doubt that the most effective outcome of such a study would be achieved when the student does entire the study herself, students also benefit from a collaboration with peers, where they form groups to do an analysis of various aspects of a same building or over a group of buildings. By integrating the respective results into a common, extensible, library, students can draw upon other results for comparisons and relationships between different aspects or buildings. The complexity this introduces is best supported in a computer medium.The Web offers many examples of architectural analyses on a wide variety of subjects. Commonly, these analyses consist of a collection of documents, categorized and hyperlinked to support navigation through the information space. More sophisticated examples rely on a database for storage and management of the data, and offer a more complex categorization of the information entities and their relationships. These studies present effective ways of accessing and browsing information, however, it is precluded within these analyses to distinguish and relate different components within the project documents. If enabled, instead, this would offer a richer information structure presenting new ways of accessing, viewing, and interpreting this information. Hereto, documents can be decomposed by content. This implies both expanding the document structure, replacing document entities by detailed substructures, and augmenting the structureis relatedness with content information. The relationships between the resulting components make the documents inherently related by content.We propose a methodology to integrate project documents into a single model, and present an application for the presentation of architectural analyses in an educational setting. This approach provides the students with a simple interface and mechanisms for the presentation of an analysis of design precedents, and possibly their own designs. Since all the information is integrated within a single environment, students will benefit from each othersi studies, and can draw new conclusions across analyses and presentations from their peers.