Circular RNAs in cancer: New insights into functions and implications in ovarian cancer

Circular RNAs (circRNAs) are a class of long non-coding RNAs (lncRNAs) which have a circular and closed loop structure. They are ubiquitous, stable, conserved and diverse RNA molecules with a range of activities such as translation and splicing regulation, which are able to interacting with RNA-binding proteins and specially miRNA sponge. The expression patterns of the circRNAs exhibited tissue specificity and also, step and stage specificity. Accumulating evidences approved the critical role of circular RNAs in many cancers such as ovarian cancer. Given that these molecules exert their effects through multiple cellular and molecular mechanisms (i.e., angiogenesis, apoptosis, growth, and metastasis) which are involved in cancer pathogenesis, circular RNAs, in particular, act by controlling cell proliferation in ovarian cancer, so that, it has been shown that the deregulation of these molecules is associated with initiation and progression of ovarian cancer. Therefore, they are attractive molecules which have introduced them as cancer biomarkers. Moreover, they could be used as new therapeutic candidates for developing novel treatment strategies. Here, for first time, we have provided a comprehensive review on the recent knowledge of circular RNAs and their pathological roles in the ovarian cancer. © 2019 The Author(s)

Expression of a large LINE-1-driven antisense RNA is linked to epigenetic silencing of the metastasis suppressor gene TFPI-2 in cancer

LINE-1 retrotransposons are abundant repetitive elements of viral origin, which in normal cells are kept quiescent through epigenetic mechanisms. Activation of LINE-1 occurs frequently in cancer and can enable LINE-1 mobilization but also has retrotransposition-independent consequences. We previously reported that in cancer, aberrantly active LINE-1 promoters can drive transcription of flanking unique sequences giving rise to LINE-1 chimeric transcripts (LCTs). Here, we show that one such LCT, LCT13, is a large transcript (>300 kb) running antisense to the metastasis-suppressor gene TFPI- 2. We have modelled antisense RNA expression at TFPI-2 in transgenic mouse embryonic stem (ES) cells and demonstrate that antisense RNA induces silencing and deposition of repressive histone modifications implying a causal link. Consistent with this, LCT13 expression in breast and colon cancer cell lines is associated with silencing and repressive chromatin at TFPI-2. Furthermore, we detected LCT13 transcripts in 56% of colorectal tumours exhibiting reduced TFPI-2 expression. Our findings implicate activation of LINE-1 elements in subsequent epigenetic remodelling of surrounding genes, thus hinting a novel retrotransposition-independent role for LINE-1 elements in malignancy

Quercetin and cancer: New insights into its therapeutic effects on ovarian cancer cells

Ovarian cancer is known as a serious malignancy that affects women's reproductive tract and can considerably threat their health. A wide range of molecular mechanisms and genetic modifications have been involved in ovarian cancer pathogenesis making it difficult to develop effective therapeutic platforms. Hence, discovery and developing new therapeutic approaches are required. Medicinal plants, as a new source of drugs, could potentially be used alone or in combination with other medicines in the treatment of various cancers such as ovarian cancer. Among various natural compounds, quercetin has shown great anti-cancer and anti-inflammatory properties. In vitro and in vivo experiments have revealed that quercetin possesses a cytotoxic impact on ovarian cancer cells. Despite obtaining good results both in vitro and in vivo, few clinical studies have assessed the anti-cancer effects of quercetin particularly in the ovarian cancer. Therefore, it seems that further clinical studies may introduce quercetin as therapeutic agent alone or in combination with other chemotherapy drugs to the clinical setting. Here, we not only summarize the anti-cancer effects of quercetin but also highlight the therapeutic effects of quercetin in the ovarian cancer. © 2020 The Author(s)

Decoupling of DNA methylation and activity of intergenic LINE-1 promoters in colorectal cancer

<p>Hypomethylation of LINE-1 repeats in cancer has been proposed as the main mechanism behind their activation; this assumption, however, was based on findings from early studies that were biased toward young and transpositionally active elements. Here, we investigate the relationship between methylation of 2 intergenic, transpositionally inactive LINE-1 elements and expression of the LINE-1 chimeric transcript (LCT) 13 and LCT14 driven by their antisense promoters (L1-ASP). Our data from DNA modification, expression, and 5′RACE analyses suggest that colorectal cancer methylation in the regions analyzed is not always associated with LCT repression. Consistent with this, in HCT116 colorectal cancer cells lacking DNA methyltransferases DNMT1 or DNMT3B, LCT13 expression decreases, while cells lacking both DNMTs or treated with the DNMT inhibitor 5-azacytidine (5-aza) show no change in LCT13 expression. Interestingly, levels of the H4K20me3 histone modification are inversely associated with LCT13 and LCT14 expression. Moreover, at these LINE-1s, H4K20me3 levels rather than DNA methylation seem to be good predictor of their sensitivity to 5-aza treatment. Therefore, by studying individual LINE-1 promoters we have shown that in some cases these promoters can be active without losing methylation; in addition, we provide evidence that other factors (e.g., H4K20me3 levels) play prominent roles in their regulation.</p

Comparison of electronic versus conventional assessment methods in ophthalmology residents; a learner assessment scholarship study

Background: Assessment is a necessary part of training postgraduate medical residents. The implementation of methods located at the �shows how� level of Miller�s pyramid is believed to be more effective than previous conventional tools. In this study, we quantitatively compared electronic and conventional methods in assessing ophthalmology residents. Methods: In this retrospective study, eight different conventional methods of assessment including residents� attendance, logbook, scholarship and research skills, journal club, outpatient department participation, Multiple Choice Question (MCQ), Objective Structured Clinical Examination (OSCE), and professionalism/360-degree (as one complex) were used to assess 24 ophthalmology residents of all grades. Electronic media consisting of an online Patient Management Problem (e-PMP), and modified electronic OSCE (me-OSCE) tests performed 3 weeks later were also evaluated for each of the 24 residents. Quantitative analysis was then performed comparing the conventional and electronic assessment tools, statistically assessing the correlation between the two approaches. Results: Twenty-four ophthalmology residents of different grades were included in this study. In the electronic assessment, average e-PMP scores (48.01 ± 12.40) were much lower than me-OSCE (65.34 ± 17.11). The total average electronic score was 56.67 ± 11.28, while the total average conventional score was 80.74 ± 5.99. Female and male residents� average scores in the electronic and conventional method were (59.15 ± 12.32 versus 83.01 ± 4.95) and (55.19 ± 10.77 versus 79.38 ± 6.29), respectively. The correlation between modified electronic OSCE and all conventional methods was not statistically significant (P-value >0.05). Correlation between e-PMP and six conventional methods, consisting of professionalism/360-degree assessment tool, logbook, research skills, Multiple Choice Questions, Outpatient department participation, and Journal club active participation was statistically significant (P-value < 0.05). The overall correlation between conventional and electronic methods was significant (P-value = 0.017). Conclusion: In this study, we conclude that electronic PMP can be used alongside all conventional tools, and overall, e-assessment methods could replace currently used conventional methods. Combined electronic PMP and me-OSCE can be used as a replacement for currently used gold-standard assessment methods, including 360-degree assessment. © 2021, The Author(s)

Highly sensitive multipoint real-time kinetic detection of Surface Plasmon bioanalytes with custom CMOS cameras

Phase sensitive Surface Plasmon Resonance (SPR) techniques are a popular means of characterizing biomolecular interactions. However, limitations due to the narrow dynamic range and difficulty in adapting the method for multi-point sensing have restricted its range of applications. This paper presents a compact phase sensitive SPR technology using a custom CMOS camera. The system is exceptionally versatile enabling one to trade dynamic range for sensitivity without altering the optical system. We present results showing sensitivity over the array of better than 10−6 Refractive Index Units (RIU) over a refractive index range of 2×10−2 RIU, with peak sensitivity of 3×10−7 RIU at the center of this range. We also explain how simply altering the settings of polarization components can give sensitivity on the order of 10−8 RIU albeit at the cost of lower dynamic range. The consistent response of the custom CMOS camera in the system also allowed us to demonstrate precise quantitative detection of two Fibrinogen antibody–protein binding sites. Moreover, we use the system to determine reaction kinetics and argue how the multipoint detection gives useful insight into the molecular binding mechanisms

Motion Rail: A Virtual Reality Level Crossing Training Application

This paper presents the development and usability testing of a Virtual Reality (VR) based system named 'Motion Rail' for training children on railway crossing safety. The children are to use a VR head mounted device and a controller to navigate the VR environment to perform a level crossing task and they will receive instant feedback on pass or failure on a display in the VR environment. Five participants consisting of two male and three females were considered for the usability test. The outcomes of the test was promising, as the children were very engaging and will like to adopt this training approach in future safety training

Rationalising the role of Keratin 9 as a biomarker for Alzheimer’s disease

Keratin 9 was recently identified as an important component of a biomarker panel which demonstrated a high diagnostic accuracy (87%) for Alzheimer’s disease (AD). Understanding how a protein which is predominantly expressed in palmoplantar epidermis is implicated in AD may shed new light on the mechanisms underlying the disease. Here we use immunoassays to examine blood plasma expression patterns of Keratin 9 and its relationship to other AD-associated proteins. We correlate this with the use of an in silico analysis tool VisANT to elucidate possible pathways through which the involvement of Keratin 9 may take place. We identify possible links with Dickkopf-1, a negative regulator of the wnt pathway, and propose that the abnormal expression of Keratin 9 in AD blood and cerebrospinal fluid may be a result of blood brain barrier dysregulation and disruption of the ubiquitin proteasome system. Our findings suggest that dysregulated Keratin 9 expression is a consequence of AD pathology but, as it interacts with a broad range of proteins, it may have other, as yet uncharacterized, downstream effects which could contribute to AD onset and progression

Inter-professional education: The necessity for ethical growth in health domain

Introduction: The necessity of closed and continuous relationships, team work and collaboration between various health professions in treatment and care have confronted health ethics with many challenges. Inter-professional education has been proposed as an effective strategy to address this gap internationally. This study has been done to determine process of ethical growth and achieving ethical competency in health sciences students during inter-professional education. Methods: This interpretive- integrative literature review study has been done in 2013 with integrative search in Pub med, CINHAL, Ovid, Science Direct data bases as well as Google scholar using key words including inter-professional education and ethics. All English language papers published between 2000 and 2013 were included. Of 155 retrieved articles, 15 documents were appropriate based on critical appraisal criteria and analyzed according to thematic synthesis method.. Then extracted text were entered and managed by MAXQDA software. Results: Promotion of professional socialization process of health sciences students”, “creating a common values system” and “forming inter-professional identity” were the three main themes emerge indicating process of ethical growth in health sciences students during inter-professional education. The themes were explained by theories such as social contact, human development, transformational learning situated learning, constructivist learning and social cognitive They are the conceptual framework in inter-professional education model. Conclusion: Inter-professional education with promotion of professional socialization process of health sciences' students, renewing and internalization of inter-professional common values and forming inter-professional identity, as complement of professional identity , empowers and enables students for effective collaboration with others. These facilitates ethical and safe performance of the graduates in clinical environments

Determining the Relationship between Dental Caries and Periodontal Disease on the Panoramic Radiographies

Introduction: Dental caries and periodontal disease are probably the most common oral chronic diseases in worldwide, and their prevalence is progressively increasing from day to day. Therefore, this study was conducted to investigate the relationship between caries and periodontal disease. Methods: In this cross sectional study, 237 panoramic radiographies of patients aged 10 to 65 years (110males and 127 females) were selected utilizing convenience sampling. In order to measure the variables, a graduate caliper with 0/2 mm accuracy and Negatoscope with optimum light were used. Moreover, in order to diagnose the caries and minimize the errors, “calibration” method was selected. Results: There was no significant relationship between crown caries and mean of alveolar bone loss. (p=0/19). As the age increased in patients, the mean of alveolar bone loss also increased and a significant association was detected between the severity of caries, alveolar bone loss and male gender. Conclusion: Generally, no relationship was observed between dental caries and periodontal disease in this study