Urtica dioica Induces Cytotoxicity in Human Prostate Carcinoma LNCaP Cells: Involvement of Oxidative Stress, Mitochondrial Depolarization and Apoptosis

Purpose: To evaluate the cytotoxic mechanisms of an extract from the leaves of the Urtica dioica (UD) plant in LNCaP prostate cancer cells.Methods: LNCaP cells were exposed to the UD extract for 24hrs and cell viability assessed using the MTT assay. Reactive oxygen species generation was assessed using the NBT assay and mitochondrial membrane potential using JCI-aggregation. DNA fragmentation patterns and cleavage of poly (ADPribose) polymerase were assessed using western blot and caspase activation via colorimetric assay.Results: The viability of LNCaP cells was significantly decreased in a dose-dependent manner following 24-h treatment with the UD extract. The reactive oxygen species levels were also significantly increased and mitochondrial depolarization was evident. DNA fragmentation, PARP cleavage and an increase in the activities of caspases 3 and 9 were observed in cells treated with the UD extract and this confirmed the induction of apoptosis as the major cytotoxic modality for this extract.Conclusion: The results confirm that the cytotoxic activity of UD aqueous extract in LNCaP cells is mediated through oxidative stress and apoptosis. These findings could hold positive implications for the potential use of UD extract in prostate cancer therapy.Keywords: Urtica dioica, Cytotoxicity, DNA fragmentation, PARP cleavage, Caspases, Prostate cance

Boundary Terms and Junction Conditions for Generalized Scalar-Tensor Theories

We compute the boundary terms and junction conditions for Horndeski's panoptic class of scalar-tensor theories, and write the bulk and boundary equations of motion in explicitly second order form. We consider a number of special subclasses, including galileon theories, and present the corresponding formulae. Our analysis opens up of the possibility of studying tunnelling between vacua in generalized scalar-tensor theories, and braneworld dynamics. The latter follows because our results are independent of spacetime dimension.Comment: 13 pages, Equation corrected. Thanks to Tsutomu Kobayashi for informing us of the typ

Towards video-based surgical workflow understanding in open orthopaedic surgery

Safe and efficient surgical training and workflow management play a critical role in clinical competency and ultimately, patient outcomes. Video data in minimally invasive surgery (MIS) have enabled opportunities for vision-based artificial intelligence (AI) systems to improve surgical skills training and assurance through post-operative video analysis and development of real-time computer-assisted interventions (CAI). Despite the availability of mounted cameras for the operating room (OR), similar capabilities are much more complex to develop for recording open surgery procedures, which has resulted in a shortage of exemplar video-based training materials. In this paper, we present a potential solution to record open surgical procedures using head-mounted cameras. Recorded videos were anonymised to remove patient and staff identifiable information using a machine learning algorithm that achieves state-of-the-art results on the OR Face dataset. We then propose a CNN-LSTM-based model to automatically segment videos into different surgical phases, which has never been previously demonstrated in open procedures. The redacted videos, along with the automatically predicted phases, are then available for surgeons and their teams for post-operative review and analysis. To our knowledge, this is the first demonstration of the feasibility of deploying camera recording systems and developing machine learning-based workflow analysis solutions for open surgery, particularly in orthopaedics

Pleosporales

One hundred and five generic types of Pleosporales are described and illustrated. A brief introduction and detailed history with short notes on morphology, molecular phylogeny as well as a general conclusion of each genus are provided. For those genera where the type or a representative specimen is unavailable, a brief note is given. Altogether 174 genera of Pleosporales are treated. Phaeotrichaceae as well as Kriegeriella, Zeuctomorpha and Muroia are excluded from Pleosporales. Based on the multigene phylogenetic analysis, the suborder Massarineae is emended to accommodate five families, viz. Lentitheciaceae, Massarinaceae, Montagnulaceae, Morosphaeriaceae and Trematosphaeriaceae

How do surgeons decide? Conduit choice in coronary artery bypass graft surgery in the UK

OBJECTIVES Conduits used in coronary artery bypass grafting may have significant impact on outcomes, but evidence is mixed and there is large variation in practice. This study provides insights into the opinions of the UK surgeons on conduit use and their decision-making processes. METHODS A questionnaire was created using the Ottawa Decision Support Framework to elicit the importance that surgeons placed on bilateral internal mammary artery grafting, skeletonization, total arterial revascularization and sequential anastomoses on a scale of 1–10. Scores ≥8 were deemed ‘important’ and ≤3 ‘not important’. Surgeons were asked to specify changes to practice in frail patients or emergencies. Additional questions included conduit type used, factors affecting decision-making and vein harvesting methods. Questionnaires were administered in person with data analysed centrally. RESULTS Ninety-seven consultant cardiac surgeons from 25 centres responded. Thirty-two percent surgeons routinely used radial arteries and 36% used right internal mammary artery. High-quality evidence contributed most to decision-making receiving a total of 328/960 points, with consultant experience being the second (255/960 points). There was a bimodal distribution of perceived importance of bilateral internal mammary artery use, with 29 (30%) ‘important’ and ‘not important’ scores each. 23% of surgeons found total arterial revascularization important. Most surgeons (64%) preferred pedicled mammary arteries. Twenty-six percent of surgeons considered sequential grafting to be important. CONCLUSIONS Low uptake of total arterial revascularization and bilateral internal mammary artery among the UK consultants may be due to the lack of high-quality evidence demonstrating a significant benefit. It is also possible that reluctance to use certain conduits may stem from low levels of exposure to conduits or inadequate training, particularly given the importance of consultant experience on decision-making

The E3 ubiquitin ligase component, Cereblon, is an evolutionarily conserved regulator of Wnt signaling

Immunomodulatory drugs (IMiDs) are important for the treatment of multiple myeloma and myelodysplastic syndrome. Binding of IMiDs to Cereblon (CRBN), the substrate receptor of the CRL4CRBN E3 ubiquitin ligase, induces cancer cell death by targeting key neo-substrates for degradation. Despite this clinical significance, the physiological regulation of CRBN remains largely unknown. Herein we demonstrate that Wnt, the extracellular ligand of an essential signal transduction pathway, promotes the CRBN-dependent degradation of a subset of proteins. These substrates include Casein kinase 1α (CK1α), a negative regulator of Wnt signaling that functions as a key component of the β-Catenin destruction complex. Wnt stimulation induces the interaction of CRBN with CK1α and its resultant ubiquitination, and in contrast with previous reports does so in the absence of an IMiD. Mechanistically, the destruction complex is critical in maintaining CK1α stability in the absence of Wnt, and in recruiting CRBN to target CK1α for degradation in response to Wnt. CRBN is required for physiological Wnt signaling, as modulation of CRBN in zebrafish and Drosophila yields Wnt-driven phenotypes. These studies demonstrate an IMiD-independent, Wnt-driven mechanism of CRBN regulation and provide a means of controlling Wnt pathway activity by CRBN, with relevance for development and disease