The Wnt-dependent signaling pathways as target in oncology drug discovery

Our current understanding of the Wnt-dependent signaling pathways is mainly based on studies performed in a number of model organisms including, Xenopus, Drosophila melanogaster, Caenorhabditis elegans and mammals. These studies clearly indicate that the Wnt-dependent signaling pathways are conserved through evolution and control many events during embryonic development. Wnt pathways have been shown to regulate cell proliferation, morphology, motility as well as cell fate. The increasing interest of the scientific community, over the last decade, in the Wnt-dependent signaling pathways is supported by the documented importance of these pathways in a broad range of physiological conditions and disease states. For instance, it has been shown that inappropriate regulation and activation of these pathways is associated with several pathological disorders including cancer, retinopathy, tetra-amelia and bone and cartilage disease such as arthritis. In addition, several components of the Wnt-dependent signaling pathways appear to play important roles in diseases such as Alzheimer’s disease, schizophrenia, bipolar disorder and in the emerging field of stem cell research. In this review, we wish to present a focused overview of the function of the Wnt-dependent signaling pathways and their role in oncogenesis and cancer development. We also want to provide information on a selection of potential drug targets within these pathways for oncology drug discovery, and summarize current data on approaches, including the development of small-molecule inhibitors, that have shown relevant effects on the Wnt-dependent signaling pathways

Social media in undergraduate medical education: A systematic review.

INTRODUCTION: There are over 3.81 billion worldwide active social media (SoMe) users. SoMe are ubiquitous in medical education, with roles across undergraduate programmes, including professionalism, blended learning, well being and mentoring. Previous systematic reviews took place before recent explosions in SoMe popularity and revealed a paucity of high-quality empirical studies assessing its effectiveness in medical education. This review aimed to synthesise evidence regarding SoMe interventions in undergraduate medical education, to identify features associated with positive and negative outcomes. METHODS: Authors searched 31 key terms through seven databases, in addition to references, citation and hand searching, between 16 June and 16 July 2020. Studies describing SoMe interventions and research on exposure to existing SoMe were included. Title, abstract and full paper screening were undertaken independently by two reviewers. Included papers were assessed for methodological quality using the Medical Education Research Study Quality Instrument (MERSQI) and/or the Standards for Reporting Qualitative Research (SRQR) instrument. Extracted data were synthesised using narrative synthesis. RESULTS: 112 studies from 26 countries met inclusion criteria. Methodological quality of included studies had not significantly improved since 2013. Engagement and satisfaction with SoMe platforms in medical education are described. Students felt SoMe flattened hierarchies and improved communication with educators. SoMe use was associated with improvement in objective knowledge assessment scores and self-reported clinical and professional performance, however evidence for long term knowledge retention was limited. SoMe use was occasionally linked to adverse impacts upon mental and physical health. Professionalism was heavily investigated and considered important, though generally negative correlations between SoMe use and medical professionalism may exist. CONCLUSIONS: Social media is enjoyable for students who may improve short term knowledge retention and can aid communication between learners and educators. However, higher-quality study is required to identify longer-term impact upon knowledge and skills, provide clarification on professionalism standards and protect against harms

Pre-administration of turmeric prevents methotrexate-induced liver toxicity and oxidative stress

Background: Methotrexate (MTX) is an antimetabolite broadly used in treatment of cancer and autoimmune diseases. MTX-induced hepatotoxicity limits its application. We investigated hepatoprotective effects of turmeric in MTX-induced liver toxicity. Methods: All experiments were performed on male Wistar albino rats that were randomly divided into six groups. Group one received saline orally for 30 days (control group), groups two and three received turmeric extract (100, 200 mg/kg respectively) orally for 30 days, group four received single dose, of MTX IP at day 30, groups five and six received turmeric extract 100 and 200 mg/kg orally respectively for 30 days and single dose of methoterxate IP (20 mg/kg) at day 30. Four days after MTX injection animals were sacrificed and evaluated. Blood ALT and AST (indicators of hepatocyte injury), ALP and bilirubin (markers of biliary function), albumin (reflect liver synthetic function) as well as the plasma TAS concentration (antioxidant defenses) were determined. The cellular antioxidant defense activities were examined in liver tissue samples using SOD, CAT, and GSH-Px for the oxidative stress, and MDA for lipid peroxidation. In addition, liver damage was evaluated histopathologically. Results: MTX significantly induced liver damage (P less than 0.05) and decreased its antioxidant capacity, while turmeric was hepatoprotective. Liver tissue microscopic evaluation showed that MTX treatment induced severe centrilobular and periportal degeneration, hyperemia of portal vein, increased artery inflammatory cells infiltration and necrosis, while all of histopathological changes were attenuated by turmeric (200 mg/kg). Conclusion: Turmeric extract can successfully attenuate MTX-hepatotoxicity. The effect is partly mediated through extracts antinflammatory activity.Funding Agencies|University of Manitoba start-up fund; Linkoping University; IGEN; Cancerfonden [2013/391]; VR-NanoVision [K2012-99X-22325-01-5]</p