Spherical Indicatrices of a Bertrand Curve in Three Lie Groups

In this paper, new representations of a Bertrand curve pair in three dimensional Lie groups with bi-invariant metric are given. Besides, the spherical indicatrices of a Bertrand curve pair are obtain and the relations between the spherical indicatrices and new representations of Bertrand curve pair are shown.Comment: 12 page

miR-17-3p Downregulates Mitochondrial Antioxidant Enzymes and Enhances the Radiosensitivity of Prostate Cancer Cells

Radioresistance remains to be a major obstacle in the management of patients with advanced prostate cancer (PCa). We have identified a mature miR-17-3p processed from the 3′ arm of precursor miR-17, which appeared to be able to inhibit three major antioxidant enzymes located in mitochondria, i.e., manganese superoxide dismutase (MnSOD), glutathione peroxidase 2 (Gpx2), and thioredoxin reductase 2 (TrxR2). Here we show that upregulation of miR-17-3p remarkably sensitized PCa cells to ionizing radiation (IR). Reductions of the three antioxidants led to increasing cellular reactive oxygen species (ROS) accumulation as well as declining mitochondrial respiration. The miR-17-3p-mediated dysfunction of mitochondrial antioxidants apparently sensitizing IR therapy was manifested in vitro and in vivo. Substantially, the miR-17-3p effect on suppression of the antioxidants can be efficiently eliminated or attenuated by transfecting with either an miR-17-3p inhibitor or each of the related antioxidant cDNA expression constructs. Overall, in addition to the insights into the functional assessments for the duplex of miR-17-5p and miR-17-3p, the present study highlights the rigorous evidence that demonstrated suppression of multiple mitochondrial antioxidants by a single microRNA (miRNA), thereby providing a promising approach to improve radiotherapy for advanced PCa by targeting mitochondrial function. Keywords: miR-17-3p, antioxidant enzymes, reactive oxygen species, radiosensitivity, prostate cance

HZ08 suppresses RelB-activated MnSOD expression and enhances Radiosensitivity of prostate Cancer cells

Abstract Background The development of radioresistance is one of main causes for therapeutic failure of prostate cancer (PCa). The present study aims to investigate the function and the related mechanism by which HZ08 sensitizes radiotherapeutic efficiency to treat aggressive PCa cells. Methods PCa cells were pretreated with HZ08 (6,7-dimethoxy-1-(3,4-dimethoxy) benzyl-2-(N-n-octyl-N′-cyano) guanyl-1,2,3,4-tetrahydroisoquinoline) and followed by ionizing radiation (IR) treatment. Cytotoxicity in the treated cells was analyzed to assess the radiosensitization capacity of HZ08 by flow cytometry, MTT and colony survival assays. The cellular levels of reactive oxygen species (ROS) and oxygen consumption rates (OCR) were measured using specific ROS detection probes and a Seahorse XF96 Analyzer, respectively. RelB binding to the NF-κB intronic enhancer region of the human SOD2 gene was determined using a ChIP assay. The levels of phosphorylation of PI3K, Akt and IKKα were quantified and further confirmed using a PI3K inhibitor. Finally, the synergistic effect of HZ08 on radiosensitization of PCa cells was validated using a mouse xenograft tumor model. Results HZ08 enhanced radiosensitivity of PCa cells through increasing ROS and declining mitochondrial respiration due to suppression of mitochondrial antioxidant enzyme MnSOD. Mechanistically, HZ08 appeared to inhibit PI3K/Akt/IKKα signaling axis, resulting in transcriptional repression of MnSOD expression by preventing RelB nuclear translocation. Conclusions HZ08 can serve as a useful radiosensitizing agent to improve radiotherapy for treating aggressive PCa cells with high level of constitutive RelB. The present study suggests a promising approach for enhancing radiotherapeutic efficiency to treat advanced PCa by inhibiting antioxidant defense function

RelB-activated GPX4 inhibits ferroptosis and confers tamoxifen resistance in breast cancer

Tamoxifen (TAM) resistance remains a major obstacle in the treatment of advanced breast cancer (BCa). In addition to the competitive inhibition of the estrogen receptor (ER) signaling pathway, damping of mitochondrial function by increasing reactive oxygen species (ROS) is critical for enhancing TAM pharmacodynamics. Here, we showed that RelB contributes to TAM resistance by inhibiting TAM-provoked ferroptosis. TAM-induced ROS level promoted ferroptosis in TAM-sensitive cells, but the effect was alleviated in TAM-resistant cells with high constitutive levels of RelB. Mechanistically, RelB inhibited ferroptosis by transcriptional upregulating glutathione peroxidase 4 (GPX4). Consequently, elevating RelB and GPX4 in sensitive cells increased TAM resistance, and conversely, depriving RelB and GPX4 in resistant cells decreased TAM resistance. Furthermore, suppression of RelB transcriptional activation resensitized TAM-resistant cells by enhancing ferroptosis in vitro and in vivo. The inactivation of GPX4 in TAM-resistant cells consistently resensitized TAM by increasing ferroptosis-mediated cell death. Together, this study uncovered that inhibition of ferroptosis contributes to TAM resistance of BCa via RelB-upregulated GPX4

Additional file 3 of HZ08 suppresses RelB-activated MnSOD expression and enhances Radiosensitivity of prostate Cancer cells

: Figure S3. The reverse effect of transfected MnSOD on cell viability of HZ08 and IR-treated cells. PC-3 (A) and DU-145 cells (B) were transfected with a MnSOD expression construct, and then treated with 5 μM HZ08 and 6 Gy IR. Cell viability was quantified by MTT. Mean ± SD was representative of three independent experiments carried out in duplication. **(P < 0.01) shows the significances between two groups as indicated. (PDF 390 kb

A framework to evaluate the interoperability of information systems – measuring the maturity of the business process alignment

In the current socio-economic environment, to face challenges such as the emergence of new technologies, globalisation and increasing demands from their clients it is inevitable that enterprises will collaborate with others and progressively shift their boundaries. In this context, interoperability has become a prerequisite in the jigsaw of such collaboration. By definition, it is entities’ ability to work together as an organisation. This ability spans a wide range of aspects, embracing both technical and business issues. Over the past decade, both the concept and the context of interoperability have been extended from a largely IT-focused domain to a business-focused domain and the evaluation of interoperability has become a rising concern. An increasing number of studies have concentrated on not just digital but business aspects of human behaviour in the social environment. In general, the wider application domain is the assessment of the interoperability of information systems and processes in any organisation (especially medium and large) that needs multiple processes to interact effectively. To deal with such concerns and pave the way to achievement of more effective collaborative goals in business, the concept of interoperability has been adopted to measure the efficiency and productivity of information systems’ integration. More than twenty approaches have so far been adopted to evaluate this interoperability, however most are unable to assess it at the higher levels, such as at the pragmatic, process and social levels. Hence, we have conducted a three-phase study. Phase 1 reviewed existing interoperability evaluation approaches. To prove the concept, phase 2 proposed the concept of semiotic interoperability and its application to healthcare information systems. This article reports on the third phase of the study, a proposed framework with a group of metrics to measure interoperability from a new perspective – a semiotics perspective. The framework is named the Semiotic Interoperability Evaluation Framework (the SIEF) and has the ability to analyse, measure and assess the interoperability among business processes. The metrics derive from a feasibility study to investigate several interoperability barriers at a hospital. Next, the SIEF was applied in a case study and a detailed interoperability evaluation was conducted