Search results for: human colorectal cancer

Authors: A. Monika, Manu Sharma, Hong Boo Lee, Richa Dhingra, Neelima Dhingra

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Nuclear factor-κappa B serve as a molecular lynchpin that links persistent infections and chronic inflammation to increased cancer risk. Inflammation has been recognized as a hallmark and cause of cancer. Natural products present a privileged source of inspiration for chemical probe and drug design. Herbal remedies were the first medicines used by humans due to the many pharmacologically active secondary metabolites produced by plants. Some of the metabolites like Lantadene (pentacyclic triterpenoids) from the weed Lantana camara has been known to inhibit cell division and showed anti-antitumor potential. The C-3 aromatic esters of lantadenes were synthesized, characterized and evaluated for cytotoxicity and inhibitory potential against Tumor necrosis factor alpha-induced activation of Nuclear factor-κappa B in lung cancer cell line A549. The 3-methoxybenzoyloxy substituted lead analogue inhibited kinase activity of the inhibitor of nuclear factor-kappa B kinase in a single-digit micromolar concentration. At the same time, the lead compound showed promising cytotoxicity against A549 lung cancer cells with IC50 ( half maximal inhibitory concentration) of 0.98l µM. Further, molecular docking of 3-methoxybenzoyloxy substituted analogue against Inhibitor of nuclear factor-kappa B kinase (Protein data bank ID: 3QA8) showed hydrogen bonding interaction involving oxygen atom of 3-methoxybenzoyloxy with the Arginine-31 and Glutamine-110. Encouraging results indicate the Lantadene’s potential to be developed as anticancer agents.

Keywords: anticancer, lantadenes, pentacyclic triterpenoids, weed

Procedia PDF Downloads 156

Authors: Amir Seyfoori, Ehsan Samiei, Mohsen Akbari

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The use of microtechnology for detection and high yield isolation of circulating tumor cells (CTCs) has shown enormous promise as an indication of clinical metastasis prognosis and cancer treatment monitoring. The Immunomagnetic assay has been also coupled to microtechnology to improve the selectivity and efficiency of the current methods of cancer biomarker isolation. In this way, generation and configuration of the local high gradient magnetic field play essential roles in such assay. Additionally, considering the intrinsic heterogeneity of cancer cells, real-time analysis of isolated cells is necessary to characterize their responses to therapy. Totally, on-chip isolation and monitoring of the specific tumor cells is considered as a pressing need in the way of modified cancer therapy. To address these challenges, we have developed a bi-layer magnetic-based microfluidic chip for enhanced CTC detection and capturing. Micromagnet arrays at the bottom layer of the chip were fabricated using a new method of magnetic nanoparticle paste deposition so that they were arranged at the center of the chain microchannel with the lowest fluid velocity zone. Breast cancer cells labelled with EPCAM-conjugated smart microgels were immobilized on the tip of the micromagnets with greater localized magnetic field and stronger cell-micromagnet interaction. Considering different magnetic nano-powder usage (MnFe2O4 & gamma-Fe2O3) and micromagnet shapes (ellipsoidal & arrow), the capture efficiency of the systems was adjusted while the higher CTC capture efficiency was acquired for MnFe2O4 arrow micromagnet as around 95.5%. As a proof of concept of on-chip tumor cell monitoring, magnetic smart microgels made of thermo-responsive poly N-isopropylacrylamide-co-acrylic acid (PNIPAM-AA) composition were used for both purposes of targeted cell capturing as well as cell monitoring using antibody conjugation and fluorescent dye loading at the same time. In this regard, magnetic microgels were successfully used as cell tracker after isolation process so that by raising the temperature up to 37⁰ C, they released the contained dye and stained the targeted cell just after capturing. This microfluidic device was able to provide a platform for detection, isolation and efficient real-time analysis of specific CTCs in the liquid biopsy of breast cancer patients.

Keywords: circulating tumor cells, microfluidic, immunomagnetic, cell isolation

Procedia PDF Downloads 143

Authors: John Hang Leung, Shyh-Yau Wang, Hei-Tung Yip, Fion, Ho Tsung-chin, Agnes LF Chan

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Objectives: Platinum-resistant ovarian cancer has a short overall survival of 9–12 months and limited treatment options. The combination of immunotherapy and targeted therapy appears to be a promising treatment option for patients with ovarian cancer, particularly to patients with platinum-resistant recurrent ovarian cancer (PRrOC). However, there are no direct head-to-head clinical trials comparing their efficacy and toxicity. We, therefore, used a network to directly and indirectly compare seven newer immunotherapies or targeted therapies combined with chemotherapy in platinum-resistant relapsed ovarian cancer, including antibody-drug conjugates, PD-1 (Programmed death-1) and PD-L1 (Programmed death-ligand 1), PARP (Poly ADP-ribose polymerase) inhibitors, TKIs (Tyrosine kinase inhibitors), and antiangiogenic agents. Methods: We searched PubMed (Public/Publisher MEDLINE), EMBASE (Excerpta Medica Database), and the Cochrane Library electronic databases for phase II and III trials involving PRrOC patients treated with immunotherapy or targeted therapy plus chemotherapy. The quality of included trials was assessed using the GRADE method. The primary outcomes compared were progression-free survival, the secondary outcomes were overall survival and safety. Results: Seven randomized controlled trials involving a total of 2058 PRrOC patients were included in this analysis. Bevacizumab plus chemotherapy showed statistically significant differences in PFS (Progression-free survival) but not OS (Overall survival) for all interested targets and immunotherapy regimens; however, according to the heatmap analysis, bevacizumab plus chemotherapy had a statistically significant risk of ≥grade 3 SAEs (Severe adverse effects), particularly hematological severe adverse events (neutropenia, anemia, leukopenia, and thrombocytopenia). Conclusions: Bevacizumab plus chemotherapy resulted in better PFS as compared with all interested regimens for the treatment of PRrOC. However, statistical differences in SAEs as bevacizumab plus chemotherapy is associated with a greater risk for hematological SAE.

Keywords: platinum-resistant recurrent ovarian cancer, network meta-analysis, immune checkpoint inhibitors, target therapy, antiangiogenic agents

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Authors: Neziha Jaouedi, Noureddine Boujnah, Mohamed Salim Bouhlel

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In the framework of human machine interaction systems enhancement, we focus throw this paper on human behavior analysis and action recognition. Human behavior is characterized by actions and reactions duality (movements, psychological modification, verbal and emotional expression). It’s worth noting that many information is hidden behind gesture, sudden motion points trajectories and speeds, many research works reconstructed an information retrieval issues. In our work we will focus on motion extraction, tracking and action recognition using wavelet network approaches. Our contribution uses an analysis of human subtraction by Gaussian Mixture Model (GMM) and body movement through trajectory models of motion constructed from kalman filter. These models allow to remove the noise using the extraction of the main motion features and constitute a stable base to identify the evolutions of human activity. Each modality is used to recognize a human action using wavelets of derived beta distributions approach. The proposed approach has been validated successfully on a subset of KTH and UCF sports database.

Keywords: feautures extraction, human action classifier, wavelet neural network, beta wavelet

Procedia PDF Downloads 411

Authors: Esra Cansever Mutlu, Muge Sennaroglu Bostan, Fatemeh Bahadori, Ebru Toksoy Oner, Mehmet S. Eroglu

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Paclitaxel is used in treatment of different cancer types mainly breast, ovarian, lung and Kaposi’s sarcoma. It is poorly soluble in water; therefore, currently used formulations tremendously show side-effects and high toxicity. Encapsulation of the drug in a nano drug carrier which causes both reducing side effects and increasing drug activity is a desired new approach for the nano-medicine to target the site of cancer. In this study, synthesis of a novel nano paclitaxel formulation made of a new amphiphilic monomer was followed by the investigation of its pharmacological properties. UV radical polymerization was carried out by using the monomer Lecithin-2-Acrylamido-2-methylpropane (L-AMPS) and the drug-spacer, to obtain sterically high stabilized, biocompatible and biodegradable phospholipid nanoparticles, in which the drug paclitaxel (Pxl) was encapsulated (NanoPxl). Particles showed high drug loading capacity (68%) and also hydrodynamic size less than 200 nm with slight negative surface charge. The drug release profile was obtained and in vitro cytotoxicity test was performed on MCF-7 cell line. Consequently, these data indicated that paclitaxel loaded Lecithin-AMPS/PCL-MAC nanoparticles can be considered as a new, safe and effective nanocarrier for the treatment of breast cancer.

Keywords: paclitaxel, nanoparticle, drug delivery, L-AMPS

Procedia PDF Downloads 320

Authors: Farrah Putri Salmanida, Mei-Li Wu, Rika Wahyuningtyas, Wen-Bin Chung, Hso-Chi Chaung, Ko-Tung Chang

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Within the field of immunotherapy, oncolytic virotherapy (OVT) employs dual approaches that directly eliminate tumor cells while preserving healthy ones and indirectly reprogram the tumor microenvironment (TME) to elicit antitumor responses. Within the TME, tumor associated macrophages (TAMs) manifest characteristics akin to those of anti-inflammatory M2 macrophages, thus earning the designation of M2-like TAMs. In prior research, two antigens denoted as A1 (g6Ld10T) and A3 (ORF6L5), derived from a complete sequence of ORF5 with partial sequence of ORF6 in Porcine Reproductive and Respiratory Syndrome Virus Genotype 2 (PRRSV-2), demonstrated the capacity to repolarize M2-type porcine alveolar macrophages (PAMs) into M1 phenotypes. In this study, we sought for utilizing OVT strategies by introducing A1 or A3 on TAMs to endow them with the anti-tumor traits of M1 macrophages while retaining their capacity to target cancer cells. Upon exposing human THP-1-derived M2 macrophages to a cross-species test with 2 µg/ml of either A1 or A3 for 24 hours, real time PCR revealed that A3, but not A1, treated cells exhibited upregulated gene expressions of M1 markers (CCR7, IL-1ß, CCL2, Cox2, CD80). These cells reacted to virus-derived antigen, as evidenced by increased expression of pattern-recognition receptors TLR3, TLR7, and TLR9, subsequently providing feedback in the form of type I interferon responses like IFNAR1, IFN-ß, IRF3, IRF7, OAS1, Mx1, and ISG15. Through an MTT assay, only after 15 µg/ml of A3 treatment could the cell viability decrease, with a predicted IC50 of 16.96 µg/ml. Interestingly, A3 caused dose-dependent toxicity to a rat C6 glial cancer cell line even at doses as low as 2.5 µg/ml and reached its IC50 at 9.419 µg/ml. Using Annexin V/7AAD staining and PCR test, we deduced that a significant proportion of C6 cells were undergoing the early apoptosis phase predominantly through the intrinsic apoptosis cascade involving Bcl-2 family proteins. Following this stage, we conducted a test on A3’s repolarization ability, which revealed a significant rise in M1 gene expression markers, such as TNF, CD80, and IL-1ß, in M2-like TAMs generated in vitro from murine RAW264.7 macrophages grown with conditioned medium of 4T1 breast cancer cells. This was corroborated by the results of transcriptome analysis, which revealed that the primary subset among the top 10 to top 30 significantly upregulated differentially expressed genes (DEGs) dominantly consisted of M1 macrophages profiles, including Ccl3, Ccl4, Csf3, TNF, Bcl6b, Stc1, and Dusp2. Our findings unveiled the remarkable potential of the PRRSV-derived antigen A3 to repolarize macrophages while also being capable of selectively inducing apoptosis in cancerous cells. While further in vivo study is needed for A3, it holds promise as an adjuvant by its dual effects in cancer therapy modalities.

Keywords: cancer cell apoptosis, interferon responses, macrophage repolarization, recombinant protein

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Authors: S. Pradhan, D. Pradhan, G. Tripathy, T. Dasmohapatra

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Suppressors of cytokine signalling (SOCS3), a newly indentified anti-apoptotic molecule is a downstream effecter of the receptor tyrosine kinase-Ras signalling pathway. Current study has uncovered that SOCS3 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. To investigate the impact of SOCS3 on MDR, we analyzed the expression of P-gp and SOCS3 by immune-histochemistry and found there was positive correlation between them. At that point we effectively interfered with RNA translation by the contamination of siRNA of SOCS3 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise the expression of P53 protein increased in a statistically significant manner (p ≤ 0.01) after RNAi exposure. Moreover, flowcytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. These outcomes proposed SOCS3 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability.

Keywords: SOCS3gene, breast cancer, multidrug resistance, MDR1 gene, RNA interference

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Authors: Yin Cheung Lam

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In 1949, the ratification of the Geneva Conventions heralded the international community’s adoption of a new universal and non-discriminatory approach to human rights in situations of conflict. However, with the proliferation of international terrorism after the 9/11 attacks on the United States (U.S.), the international community’s uneven and contradictory implementations of international humanitarian law (IHL) questioned its agenda of universal human rights. Specifically, the derogation from IHL has never been so pronounced in the U.S. led ‘War on Terror’. While an extensive literature has ‘assessed the impact’ of the implementation of the Geneva Conventions, limited attention has been paid to interrogating the ways in which the Geneva Conventions and its resulting implementation have functioned to discursively reproduce certain understandings of human rights between states and non-state actors. Through a discursive analysis of the Geneva Conventions and the conceptualization of human rights in relation to terrorism, this thesis problematises the way in which the U.S. has understood and reproduced understandings of human rights. Using the U.S. ‘War on Terror’ as an example, it seeks to extend previous analyses of the U.S.’ practice of IHL through a qualitative discursive analysis of the human rights content that appears in the Geneva Conventions in addition to the speeches and policy documents on the ‘War on Terror’.

Keywords: discursive analysis, human rights, non-state actors, war on terror

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Authors: Jiahe Liu, Hongyang Yu, Feng Qian, Miao Luo

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SMPL-X was a powerful parametric human body model that included male, neutral, and female models, with significant gender differences between these three models. During the process of 3D human body reconstruction, the correct selection of standard templates was crucial for obtaining accurate results. To address this issue, we developed an efficient gender classification algorithm to automatically select the appropriate template for 3D human body reconstruction. The key to this gender classification algorithm was the precise analysis of human body features. By using the SMPL-X model, the algorithm could detect and identify gender features of the human body, thereby determining which standard template should be used. The accuracy of this algorithm made the 3D reconstruction process more accurate and reliable, as it could adjust model parameters based on individual gender differences. SMPL-X and the related gender classification algorithm have brought important advancements to the field of 3D human body reconstruction. By accurately selecting standard templates, they have improved the accuracy of reconstruction and have broad potential in various application fields. These technologies continue to drive the development of the 3D reconstruction field, providing us with more realistic and accurate human body models.

Keywords: gender classification, joint detection, SMPL-X, 3D reconstruction

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Authors: Priya Patel, Paresh Patel, Mihir Raval

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Silibinin, a flavanone as an antimicrotubular agent used in the treatment of cancer, was encapsulated in nanoparticles (NPs) of poly (lactide-co-glycolide) (PLGA) polymer using the spray-drying technique. The effects of various experimental parameters were optimized by box-behnken experimental design. Production yield, encapsulation efficiency and dissolution study along with characterization by scanning electron microscopy, DSC, FTIR followed by bioavailability study. Particle size and zeta potential were evaluated by using zetatrac particle size analyzer. Experimental design it was evaluated that inlet temperature and polymer concentration influence on the drug release. Feed flow rate impact on particle size. Results showed that spray drying technique yield 149 nm indicate nanosize range. The small size of the nanoparticle resulted in an enhanced cellular entry and greater bioavailability. Entrapment efficiency was found between 89.35% and 98.36%. Zeta potential shows good stability index of nanoparticle formulation. The in vitro release studies indicated the silibinin loaded PLGA nanoparticles provide controlled drug release over a period of 32 h. Pharmacokinetic studies demonstrated that after oral administration of silibinin-loaded PLGA nanoparticles to rats at a dose of 10 mg/kg, relative bioavailability was enhanced about 8.85-fold, compared to silibinin suspension as control hence, this investigation demonstrated the potential of the experimental design in understanding the effect of the formulation variables on the quality of silibinin loaded PLGA nanoparticles. These results describe an effective strategy of silibinin loaded PLGA nanoparticles and might provide a promising approach against the cancer.

Keywords: silibinin, cancer, nanoparticles, PLGA, bioavailability

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Authors: Stephanie K. Douglas, Gordon R. Haley

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Organizations face increasing disruptions, changes, and uncertainties through the rapid shifts in the economy and business environment. A capacity for resilience is necessary for organizations to survive and thrive in such adverse conditions. Learning is an essential component of an organization's capability for building resilience. Strategic human resource management is a principal component of learning and organizational resilience. To achieve organizational resilience, human resource management strategies must support individual knowledge, skills, and ability development through organizational learning. This study aimed to contribute to the comprehensive knowledge of the relationship between strategic human resource management and organizational learning to build organizational resilience. The organizational learning dimensions of knowledge acquisition, knowledge distribution, knowledge interpretation, and organizational memory can be fostered through human resource management strategies and then aggregated to the organizational level to build resilience.

Keywords: human resource development, human resource management, organizational learning, organizational resilience

Procedia PDF Downloads 137

Authors: Emmanouel Koumoulas, Aikaterini Rokkou, Marios Moschakis

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Theagenio" in Thessaloniki exists and works for three centuries now as a hospital. Since 1975, it has been operating as an Integrated Special Cancer Hospital and since 1985 it has been integrated into the National Health System. "Theagenio" Cancer Hospital is located at the central web of Thessaloniki residential complex and consists of two buildings, the "Symeonidio Research Center", which was completed in 1962 and the Nursing Ward, a project that was later completed in 1975. This paper examines the design of the Hospital Unit according to the requirements of the energy design of buildings. Initially, the energy characteristics of the Hospital are recorded, followed by a detailed presentation of the electromechanical installations. After the existing situation has been captured and with the help of the software TEE-KENAK, different scenarios for the energy upgrading of the buildings have been studied. Proposals for upgrading concern both the shell, e.g. installation of external thermal insulation, replacement of frames, addition of shading systems, etc. as well as electromechanical installations, e.g. use of ceiling fans, improvements in heating and cooling systems, interventions in lighting, etc. The simulation calculates the future energy status of the buildings and presents the economic benefits of the proposed interventions with reference to the environmental profits that arise.

Keywords: energy consumption in hospitals, energy saving interventions, energy upgrading, hospital facilities

Procedia PDF Downloads 152

Authors: Lottie Lane

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It is habitually assumed and stated that the World Bank should engage and comply with international human rights standards. However, the basis for holding the Bank to such standards is unclear. Most advocates of the idea invoke aspects of international law to argue that the Bank has existing obligations to act in compliance with human rights standards. The Bank itself, however, does not appear to accept such arguments, despite having endorsed the importance of human rights for a considerable length of time. A substantial challenge is that under the current international human rights law framework, the World Bank is considered a non-state actor, and as such, has no direct human rights obligations. In the absence of clear legal duties for the Bank, it is necessary to look at the tools available beyond the international human rights framework to encourage the Bank to comply with human rights standards. This article critically examines several bases for arguing that the Bank should comply and engage with human rights through its policies and practices. Drawing on the Bank’s own ‘good governance’ approach as well as the United Nations’ ‘human rights-based-approach’ to development, a new basis is suggested. First, the relationship between the World Bank and human rights is examined. Three perspectives are considered: (1) the legal position – what the status of the World Bank is under international human rights law, and whether it can be said to have existing legal human rights obligations; (2) the Bank’s own official position – how the Bank envisages its relationship with and role in the protection of human rights; and (3) the relationship between the Bank’s policies and practices and human rights (including how its attitudes are reflected in its policies and how the Bank’s operations impact human rights enjoyment in practice). Here, the article focuses on two examples – the (revised) 2016 Environmental and Social Safeguard Policies and the 2012 case-study regarding Gambella, Ethiopia. Both examples are widely considered missed opportunities for the Bank to actively engage with human rights. The analysis shows that however much pressure is placed on the Bank to improve its human rights footprint, it is extremely reluctant to do so explicitly, and the legal bases available are insufficient for requiring concrete, ex ante action by the Bank. Instead, the Bank’s own ‘good governance’ approach to development – which it has been advocating since the 1990s – can be relied upon. ‘Good governance’ has been used and applied by many actors in many contexts, receiving numerous different definitions. This article argues that human rights protection can now be considered a crucial component of good governance, at least in the context of development. In doing so, the article explains the relationship and interdependence between the two concepts, and provides three rationales for the Bank to take a ‘human rights-based approach’ to good governance. Ultimately, this article seeks to look beyond international human rights law and take a governance approach to provide a convincing basis upon which to argue that the World Bank should comply with human rights standards.

Keywords: World Bank, international human rights law, good governance, human rights-based approach

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Authors: Shirui Huang, Wei Chen, Chuanshu Huang

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Basal muscle-invasive bladder cancer (BMIBC) is considered one of the subtypes of BC with the highest metastatic rate and the poorest prognosis. Therefore, elucidating the mechanisms underlying BMIBC metastasis and identifying novel precision therapeutic targets are current research hotspots and challenges to cancer researchers. Through a series of in vitro and in vivo functional experiments, we have identified the crucial role of KRT14 in the high invasiveness and adverse prognosis of BMIBC. We found that the K294 site within the IGF2BP1-KH2 domain is responsible for reading the conserved genetic information carried by D226/E227 in the KRT14 nuclear export signal (NES). Activation of the KRT14-IGF2BP1 signaling axis is essential for IGF2BP1-mediated stabilization of SNAI1 mRNA through FTO modification. Additionally, IGF2BP1 forms a positive feedback loop by stabilizing its own mRNA, thereby accelerating the invasion and metastasis of BMIBC. Collectively, our study identifies the KRT14/IGF2BP1/FTO/Snail signaling axis as an essential regulatory mechanism associated with poor prognosis in BMIBC, providing a theoretical basis for KRT14 and its downstream regulated molecules as therapeutic targets for BMIBC and the development of corresponding targeted therapies.

Keywords: BMIBC, KRT4, IFGF2BP1, DNA methylation

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Authors: Ankan Roy, Niharika, Samir Kumar Patra

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Anomalous nexus of complex topological assemblies and spatiotemporal epigenetic choreography at chromosomal territory may forms the most sophisticated regulatory layer of gene expression in cancer. Colon cancer is one of the leading malignant neoplasms of the lower gastrointestinal tract worldwide. There is still a paucity of information about the complex molecular mechanisms of colonic cancerogenesis. Bioinformatics prediction and analysis helps to identify essential genes and significant pathways for monitoring and conquering this deadly disease. The present study investigates and explores potential hub genes as biomarkers and effective therapeutic targets for colon cancer treatment. Colon cancer patient sample containing gene expression profile datasets, such as GSE44076, GSE20916, and GSE37364 were downloaded from Gene Expression Omnibus (GEO) database and thoroughly screened using the GEO2R tool and Funrich software to find out common 2 differentially expressed genes (DEGs). Other approaches, including Gene Ontology (GO) and KEGG pathway analysis, Protein-Protein Interaction (PPI) network construction and hub gene investigation, Overall Survival (OS) analysis, gene correlation analysis, methylation pattern analysis, and hub gene-Transcription factors regulatory network construction, were performed and validated using various bioinformatics tool. Initially, we identified 166 DEGs, including 68 up-regulated and 98 down-regulated genes. Up-regulated genes are mainly associated with the Cytokine-cytokine receptor interaction, IL17 signaling pathway, ECM-receptor interaction, Focal adhesion and PI3K-Akt pathway. Downregulated genes are enriched in metabolic pathways, retinol metabolism, Steroid hormone biosynthesis, and bile secretion. From the protein-protein interaction network, thirty hub genes with high connectivity are selected using the MCODE and cytoHubba plugin. Survival analysis, expression validation, correlation analysis, and methylation pattern analysis were further verified using TCGA data. Finally, we predicted COL1A1, COL1A2, COL4A1, SPP1, SPARC, and THBS2 as potential master regulators in colonic cancerogenesis. Moreover, our experimental data highlights that disruption of lipid raft and RAS/MAPK signaling cascade affects this gene hub at mRNA level. We identified COL1A1, COL1A2, COL4A1, SPP1, SPARC, and THBS2 as determinant hub genes in colon cancer progression. They can be considered as biomarkers for diagnosis and promising therapeutic targets in colon cancer treatment. Additionally, our experimental data advertise that signaling pathway act as connecting link between membrane hub and gene hub.

Keywords: hub genes, colon cancer, DNA methylation, epigenetic engineering, bioinformatic predictions

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Authors: Yustina Trihoni Nalesti Dewi

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Gross violations of human rights consisting of crime against humanity, genocide and war crime, are serious international crimes. Prohibition such crimes have obtain to the level of international norms of jus cogens based on conventions and customary international law. Therefore, the duty of the state to punish the crimes is obligatory. The legal consequence of jus cogens is obligation erga omnes which are a matter of state responsibility. When a state is not willing or neglects to do so in its national law, it results in state responsibility to be imposed by international human rights and humanitarian law. This article reviews the concept of jus cogens and obligatio erga omnes that appear as two sides of the same coin. It also explains how international human rights and humanitarian law set down the duty of the state to punish gross violations of human rights.

Keywords: duty of states, gross violations of human rights, jus cogens, obligatio erga omnes

Procedia PDF Downloads 471

Authors: J. F. Pollo Gaspary, F. Peron Gaspary, E. M. Simão, R. Concatto Beltrame, G. Orengo de Oliveira, M. S. Ristow Ferreira, F. Sartori Thies, I. F. Minello, F. dos Santos de Oliveira

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Background: The immune system has evolved several mechanisms to protect the host against cancer, and it has now been suggested that the expansion of its functions may prevent tumor growth and control the symptoms of cancer patients. Two techniques, ozone therapy and pulsed electromagnetic fields (PEMF), are independently associated with an increase in the immune system functions and they maybe help palliative care of patients in these conditions. Case Report: A patient with rectal adenocarcinoma with metastases decides to interrupt the clinical chemotherapy protocol due to refractoriness and side effects. As a palliative care alternative treatment it is suggested to the patient the use of ozone therapy associated with PEMF techniques. Results: The patient reports an improvement in well-being, in autonomy and in pain control. Imaging tests confirm a pause in tumor growth despite more than 60 days without using classic treatment. These results associated with palliative care alternative treatment stimulate the return to the chemotherapy protocol. Discussion: This case illustrates that these two techniques can contribute to the control of tumor growth and refractory symptoms, such as pain, probably by enhancing the immune system. Conclusions: The potential use of the combination of these two therapies, ozone therapy and PEMF therapy, can contribute to palliation of cancer patients, alone or in combination with pharmacological therapies. The conduct of future investigations on this paradigm can elucidate how much these techniques contribute to the survival and well-being of these patients.

Keywords: cancer, complementary and alternative medicine , ozone therapy, palliative care, PEMF therapy

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Authors: Chi-Ching Lee, Po-Jung Huang, Kuo-Yang Huang, Petrus Tang

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Background: Recent advances in high-throughput research technologies such as new-generation sequencing and multi-dimensional liquid chromatography makes it possible to dissect the complete transcriptome and proteome in a single run for the first time. However, it is almost impossible for many laboratories to handle and analysis these “BIG” data without the support from a bioinformatics team. We aimed to provide a web-based analysis platform for users with only limited knowledge on bio-computing to study the functional genomics and proteomics. Method: We use NCI-60 as an example dataset to demonstrate the power of the web-based analysis platform and data delivering system: C-eXpress takes a simple text file that contain the standard NCBI gene or protein ID and expression levels (rpkm or fold) as input file to generate a distribution map of gene/protein expression levels in a heatmap diagram organized by color gradients. The diagram is hyper-linked to a dynamic html table that allows the users to filter the datasets based on various gene features. A dynamic summary chart is generated automatically after each filtering process. Results: We implemented an integrated database that contain pre-defined annotations such as gene/protein properties (ID, name, length, MW, pI); pathways based on KEGG and GO biological process; subcellular localization based on GO cellular component; functional classification based on GO molecular function, kinase, peptidase and transporter. Multiple ways of sorting of column and rows is also provided for comparative analysis and visualization of multiple samples.

Keywords: cancer, visualization, database, functional annotation

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Authors: Ruqayya Naheed Khan, Awais Amjad Malik, Awais Naeem, Amina Khan, Asad Parvaiz

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Introduction: Axillary nodal status in breast cancer patients is a paramount prognosticator, next to primary tumor size and grade. It has been well established that patients with negative sentinel lymph node biopsy can safely avoid axillary lymph node dissection. A positive sentinel lymph node has traditionally required subsequent axillary dissection. According to ACOSOG Z11 trial, patients who underwent axillary dissection with 3 or more positive sentinel nodes or opted for observation in case of negative sentinel lymph node, did not find any difference in Overall Survival (OS) and Disease Free Survival (DFS). The Z11 trial included patients who underwent breast conserving surgery and excluded patients with mastectomies. The purpose of this study is to determine whether Z0011 can be applied to mastectomy patients as well in 1-3 positive sentinel lymph nodes and avoid unnecessary ALND. Methods: A retrospective review was conducted at Shaukat Khanam Memorial Cancer Hospital Pakistan from Jan 2015 to Dec 2017 including patients who were treated for invasive breast cancer and required upfront mastectomy. They were clinically node negative, so sentinel lymph node biopsy was performed. Patients underwent ALND with positive sentinel lymph node. A total of 156 breast cancer patients with mastectomies were reviewed. Results: 95% of the patients were female while 3% were male. Average age was 44 years. There was no difference in race, comorbidities, histology, T stage, N stage, and overall stage, use of adjuvant chemotherapy and radiation therapy. 64 patients underwent ALND for positive lymph node while 92 patients were spared of axillary dissection due to negative sentinel lymph node biopsy. Out of 64 patients, 38 patients (59%) had only 1 lymph node positive which was the sentinel node. 18 patients (28%) had 2 lymph nodes positive including the sentinel node while only 8 patients (13%) had 3 or more positive nodes. Conclusion: Keeping in mind the complications related to ALND, above results clearly show that ALND could have been avoided in 87% of patients in the setting of adjuvant radiation, possibly avoiding the morbidity associated with axillary lymphadenectomy although a prospective randomized trial needs to confirm these results.

Keywords: mastectomy, sentinel lymph node biopsy, axillary lymph node dissection, breast cancer

Procedia PDF Downloads 195

Authors: Yrfet Shkreli

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To determine the content of human rights norms in national constitutions, international law - in the form of treaties, declarations and case law from international monitoring bodies, and comparative case law from other countries - is often discussed in the judgments of domestic courts. This paper explores the extent to which international law has influenced domestic human rights case law in Africa. The paper first explores how the human rights provisions of African constitutions came into being before turning to the role played by international law in the constitutional order of various African states and how treaties, declarations and findings of international monitoring bodies have been used in African countries to interpret and expand on constitutional human rights provisions.

Keywords: European Union, global governance, globalization, normative power

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Authors: Sutinon Yuchomsuk, Satchachon Changthom, Pruet Areesawangvong, Monsiri Jinapen

Abstract:

Background: Esophageal squamous cell carcinoma can be presented with many symptoms, such as dysphagia or weight loss. However, in some circumstances, rare presentations can be found, e.g., dyspnea, which is more common in pulmonary malignancy. And dyspnea is also one of the most common presentations of COVID-19 infection. So, in this case, we can learn from many points in patient symptoms and findings leading to the diagnosis of esophageal squamous cell carcinoma. Method: This research is a case-report study including one patient from Mahasarakham Hospital, Thailand. Data were collected during December 2021. Result: A 55-year-old Thai male patient with an unknown past medical history presented with dyspnea and shortness of breath for the duration of three days prior to admission. His symptom also included cough, fever, and sore throat. Laboratory results indicated that the patient had COVID-19 pneumonia. Further investigation showed that he had cardiac tamponade and suspected pulmonary/esophageal cancer. Lung biopsy and pericardiocentesis were done, which were positive for carcinoma from pericardial effusion but negative for malignancy from the lung biopsy. Later esophagogastroduodenoscopy was done with endoscopic tissue biopsy; the result was positive for squamous cell carcinoma of the esophagus. Conclusion: Most commonly, esophageal cancer is presented with dysphagia or weight loss. However, in some rare cases, patients can also be presented with dyspnea due to cardiac tamponade. And in recent years, COVID-19 has become a pandemic all over the world, sometimes masking symptoms of other diseases. Such as in this case, the patient didn’t improve after the pneumonia was resolved, which led to the final diagnosis of metastatic esophageal cancer.

Keywords: esophageal cancer, cardiac tamponade, metastatic squamous cell carcinoma, COVID-19 infection

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Authors: Elsie M. Nolte, Annie M. Joubert, Roy Lakier, Maryke Etsebeth, Jolene M. Helena, Marcel Verwey, Laurence Lafanechere, Anne E. Theron

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Treatment regimens for breast- and lung cancers may include both radiation- and chemotherapy. Ideally, a pharmaceutical agent which selectively sensitizes cancer cells to gamma (γ)-radiation would allow administration of lower doses of each modality, yielding synergistic anti-cancer benefits and lower metastasis occurrence, in addition to decreasing the side-effect profiles. A range of 2-methoxyestradiol (2-ME) analogues, namely 2-ethyl-3-O-sulphamoyl-estra-1,3,5 (10) 15-tetraene-3-ol-17one (ESE-15-one), 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol) and 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16) were in silico-designed by our laboratory, with the aim of improving the parent compound’s bioavailability in vivo. The main effect of these compounds is the disruption of microtubule dynamics with a resultant mitotic accumulation and induction of programmed cell death in various cancer cell lines. This in vitro study aimed to determine the cellular responses involved in the radiation sensitization effects of these analogues at low doses in breast- and lung cancer cell lines. The oestrogen receptor positive MCF-7-, oestrogen receptor negative MDA-MB-231- and triple negative BT-20 breast cancer cell lines as well as the A549 lung cancer cell line were used. The minimal compound- and radiation doses able to induce apoptosis were determined using annexin-V and cell cycle progression markers. These doses (cell line dependent) were used to pre-sensitize the cancer cells 24 hours prior to 6 gray (Gy) radiation. Experiments were conducted on samples exposed to the individual- as well as the combination treatment conditions in order to determine whether the combination treatment yielded an additive cell death response. Morphological studies included light-, fluorescence- and transmission electron microscopy. Apoptosis induction was determined by flow cytometry employing annexin V, cell cycle analysis, B-cell lymphoma 2 (Bcl-2) signalling, as well as reactive oxygen species (ROS) production. Clonogenic studies were performed by allowing colony formation for 10 days post radiation. Deoxyribonucleic acid (DNA) damage was quantified via γ-H2AX foci and micronuclei quantification. Amplification of the p53 signalling pathway was determined by western blot. Results indicated that exposing breast- and lung cancer cells to nanomolar concentrations of these analogues 24 hours prior to γ-radiation induced more cell death than the compound- and radiation treatments alone. Hypercondensed chromatin, decreased cell density, a damaged cytoskeleton and an increase in apoptotic body formation were observed in cells exposed to the combination treatment condition. An increased number of cells present in the sub-G1 phase as well as increased annexin-V staining, elevation of ROS formation and decreased Bcl-2 signalling confirmed the additive effect of the combination treatment. In addition, colony formation decreased significantly. p53 signalling pathways were significantly amplified in cells exposed to the analogues 24 hours prior to radiation, as was the amount of DNA damage. In conclusion, our results indicated that pre-treatment of breast- and lung cancer cells with low doses of 2-ME analogues sensitized breast- and lung cancer cells to γ-radiation and induced apoptosis more so than the individual treatments alone. Future studies will focus on the effect of the combination treatment on non-malignant cellular counterparts.

Keywords: cancer, microtubule dynamics, radiation therapy, radiosensitization

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Authors: Briohny H. Spencer, Russ Chess-Williams, Catherine McDermott, Shailendra Anoopkumar-Dukie, David Christie

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Background: Prostate cancer is the second most common cancer diagnosed in men worldwide and the most prevalent in Australian men. In 2015, it was estimated that approximately 18,000 new cases of prostate cancer were diagnosed in Australia. Currently, for localised disease, androgen depravation therapy (ADT) and radiotherapy are a major part of the curative management of prostate cancer. ADT acts to reduce the levels of circulating androgens, primarily testosterone and the locally produced androgen, dihydrotestosterone (DHT), or by preventing the subsequent activation of the androgen receptor. Thus, the growth of the cancerous cells can be reduced or ceased. Radiation techniques such as brachytherapy (radiation delivered directly to the prostate by transperineal implant) or external beam radiation therapy (exposure to a sufficient dose of radiation aimed at eradicating malignant cells) are also common techniques used in the treatment of this condition. Radiotherapy (RT) has significant limitations, including reduced effectiveness in treating malignant cells present in hypoxic microenvironments leading to radio-resistance and poor clinical outcomes and also the significant side effects for the patients. Alpha1-adrenoceptor antagonists are used for many prostate cancer patients to control lower urinary tract symptoms, due to the progression of the disease itself or may arise as an adverse effect of the radiotherapy treatment. In Australia, a significant number (not a majority) of patients receive a α1-ADR antagonist and four drugs are available including prazosin, terazosin, alfuzosin and tamsulosin. There is currently limited published data on the effects of α1-ADR antagonists during radiotherapy, but it suggests these medications may improve patient outcomes by enhancing the effect of radiotherapy. Aim: To determine the impact of α1-ADR antagonists treatments on time to biochemical relapse following radiotherapy. Methods: A retrospective study of male patients receiving radiotherapy for biopsy-proven localised prostate cancer was undertaken to compare cancer outcomes for drug-naïve patients and those receiving α1-ADR antagonist treatments. Ethical approval for the collection of data at Genesis CancerCare QLD was obtained and biochemical relapse (defined by a PSA rise of >2ng/mL above the nadir) was recorded in months. Rates of biochemical relapse, prostate specific antigen doubling time (PSADT) and Kaplan-Meier survival curves were also compared. Treatment groups were those receiving α1-ADR antagonists treatment before or concurrent with their radiotherapy. Data was statistically analysed using One-way ANOVA and results expressed as mean ± standard deviation. Major findings: The mean time to biochemical relapse for tamsulosin, prazosin, alfuzosin and controls were 45.3±17.4 (n=36), 41.5±19.6 (n=11), 29.3±6.02 (n=6) and 36.5±17.6 (n=16) months respectively. Tamsulosin, prazosin but not alfuzosin delayed time to biochemical relapse although the differences were not statistically significant. Conclusion: Preliminary data for the prior and/or concurrent use of tamsulosin and prazosin showed a positive trend in delaying time to biochemical relapse although no statistical significance was shown. Larger clinical studies are indicated and with thousands of patient records yet to be analysed, it may determine if there is a significant effect of these drugs on control of prostate cancer.

Keywords: alpha1-adrenoceptor antagonists, biochemical relapse, prostate cancer, radiotherapy

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Authors: Sudeshna Mukherjee, Leena Fageria, R. Venkataramana Dilip, Rajdeep Chowdhury, Jitendra Panwar

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Metal nanoparticles in recent years have gained importance in cancer therapy due to their enhanced permeability retention effect. Among various nanomaterials, silver nanoparticles (AgNPs) have received considerable attention due to their unique properties like conductivity, chemical stability, relative lower toxicity and outstanding therapeutic potential, such as anti-inflammatory, antimicrobial and anti-cancerous activities. In this study, we took a greener approach to synthesize silver nanoparticle from fungus and analyze its effects on both epithelial and mesenchymal derived cancer cells. Much research has been done on nanoparticle-induced apoptosis, but little is known about its role in autophagy. In our study, the silver nanoparticles were seen to induce autophagy which was analyzed by studying the expression of several autophagy markers like, LC3B-II and ATG genes. Monodansylcadaverine (MDC) assay also revealed the induction of autophagy upon treatment with AgNPs. Inhibition of autophagy by chloroquine resulted in increased cell death suggesting autophagy as a survival strategy adopted by the cells. In parallel to autophagy induction, silver nanoparticles induced ROS accumulation. Interestingly, autophagy inhibition by chloroquine increased ROS level, resulting in enhanced cell death. We further analyzed MAPK signaling upon AgNP treatment. It was observed that along with autophagy, activation of JNK signaling served as pro-survival while ERK signaling served as a pro-death signal. Our results provide valuable insights into the role of autophagy upon AgNP exposure and provide cues to probabilistic strategies to effectively sensitize cancer cells.

Keywords: autophagy, JNK signalling, reactive oxygen species, silver nanoparticles

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Authors: Rostyslav Horbay, Nick Korolis, Vahid Anvari, Rostyslav Stoika

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Introduction: Giant cancer cells (GCC) are common in all types of cancer, especially after poor therapy. Some specific features of such cells include ~10-fold enlargement, drug resistance, and the ability to propagate similar daughter cells. We used murine NK/Ly lymphoma, an aggressive and fast growing lymphoma model that has already shown drastic changes in GCC comparing to parental cells (chromatin condensation, nuclear fragmentation, tighter OXPHOS/cellular respiration coupling, multidrug resistance). Materials and methods: In this study, we compared morpho-functional changes of GCC that predominantly show either a cytostatic or a cytotoxic effect after treatment with drugs. We studied the effect of a combined cytostatic/cytotoxic drug treatment to determine the correlation of drug efficiency and GCC formation. Doses of G1/S-specific drug paclitaxel/PTX (G2/M-specific, 50 mg/mouse), vinblastine/VBL (50 mg/mouse), and DNA-targeting agents doxorubicin/DOX (125 ng/mouse) and cisplatin/CP (225 ng/mouse) on C57 black mice. Several tests were chosen to estimate morphological and physiological state (propidium iodide, Rhodamine-123, DAPI, JC-1, Janus Green, Giemsa staining and other), which included cell integrity, nuclear fragmentation and chromatin condensation, mitochondrial activity, and others. A single and double factor ANOVA analysis were performed to determine correlation between the criteria of applied drugs and cytomorphological changes. Results: In all cases of treatment, several morphological changes were observed (intracellular vacuolization, membrane blebbing, and interconnected mitochondrial network). A lower gain in ascites (49.97% comparing to control group) and longest lifespan (22+9 days) after tumor injection was obtained with single VBL and single DOX injections. Such ascites contained the highest number of GCC (83.7%+9.2%), lowest cell count number (72.7+31.0 mln/ml), and a strong correlation coefficient between increased mitochondrial activity and percentage of giant NK/Ly cells. A high number of viable GCC (82.1+9.2%) was observed compared to the parental forms (15.4+11.9%) indicating that GCC are more drug resistant than the parental cells. All this indicates that the giant cell formation and its ability to obtain drug resistance is an expanding field in cancer research.

Keywords: ANOVA, cisplatin, doxorubicin, drug resistance, giant cancer cells, NK/Ly lymphoma, paclitaxel, vinblastine

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Authors: Liang Ning, Chung Hau Yin

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Angiogenesis is the process of new blood vessel development. It has been recognized as a therapeutic target for blocking cancer growth four decades ago. Vascular sprouting is initiated by pro-angiogenic factors. Vascular endothelial cell growth factor (VEGF) plays a central role in angiogenic initiation, many patients with cancer or ocular neovascularization have been benefited from anti-VEGF therapy. Emerging approaches impacting in the later stages of vessel remodeling and maturation are expected to improve clinical efficacy. TIE receptor as well as the corresponding angiopoietin ligands, were identified as another endothelial cell specific receptor tyrosine kinase signaling system. Much efforts were made to reduce the activity of angiopoietin-TIE receptor axis. Two eudesmane-type sesquiterpenes from laggera alata, namely, 15-dihydrocostic acid and ilicic acid were found with strong anti-angiogenic properties in zebrafish model. Meanwhile, the mRNA expression levels of VEGFR2 and TIE2 pathway related genes were down-regulated in the sesquiterpenes treated zebrafish embryos. Besides, in human umbilical vein endothelial cells (HUVECs), the sesquiterpenes have the ability to inhibit VEGF-induced HUVECs proliferation and migration at non-toxic concentration. Moreover, angiopoietin-2 induced TIE2 phosphorylation was inhibited by the sesquiterpenes, the inhibitory effect was detected in angiopoietin-1 induced HUVECs proliferation as well. Thus, we hypothesized the anti-angiogenic activity of the compounds may via the inhibition of VEGF and TIE2 related pathways. How the compounds come into play as the pathways inhibitors need to be evaluated in the future.

Keywords: Laggera alata, eudesmane-type sesquiterpene, anti-angiogenesis, VEGF, angiopoietin, TIE2

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Authors: Luna Shamieh

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Various players are part of the game in an asymmetric war, all making efforts to provide human security to their own adherents. Although a fragile state is not able to provide sufficient and comprehensive services, it still provides special services and security to the elite; the insurgents as well provide services and security to their associates. The humanitarian organisations, on the other hand, provide some fundamental elements of human security, but only in the regions, they are able to access when possible (if possible). The counterinsurgents (security forces of the state and intervention forces) operate within a narrow band defined by the vision of the responsibility to protect and the perspective of the resolution of the conflict through combat; hence, the possibility to provide human security is shaken at this end. This article examines how each player provides human security from the perspective of freedom from want in order to secure basic and strategic needs, freedom from fear through providing protection against all kinds of violence, and the freedom to live in dignity. It identifies a vicious cycle caused by the intervention of the different players causing a centrifugal force that may lead to disintegration of the nation under war.

Keywords: asymmetric war, counterinsurgency, fragile state, human security, insurgency

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Authors: M. R. Vijayakumar, K. Priyanka, Ramoji Kosuru, Lakshmi, Sanjay Singh

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Trans resveratrol (RES) is a non-flavonoid poly-phenolic compound proved for its therapeutic and preventive effect against various types of cancer. However, the practical application of RES in cancer treatment is limited because of its higher dose (up to 7.5 g/day in humans), low biological half life, rapid metabolism and faster elimination in mammals. PEGylated core-shell type lipid polymer hybrid nanoparticles are the novel drug delivery systems for long circulation and improved anti cancer effect of its therapeutic payloads. Therefore, the main objective of this study is to extend the biological half life (long circulation) and improve the therapeutic efficacy of RES through core shell type of nanoparticles. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS), a novel surfactant is applied for the preparation of PEGylated lipid polymer hybrid nanoparticles. The prepared nanoparticles were evaluated by various state of the art techniques such as dynamic light scattering (DLS) technique for particle size and zeta potential, TEM for shape, differential scanning calorimetry (DSC) for interaction analysis and XRD for crystalline changes of drug. Entrapment efficiency and invitro drug release were determined by ultracentrifugation method and dialysis bag method, respectively. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies after i.v administration were performed in sprague dawley rats. The prepared NPs were found to be spherical in shape with smooth surfaces. Particle size and zeta potential of prepared NPs were found to be in the range of 179.2±7.45 to 266.8±9.61 nm and -0.63 to -48.35 mV, respectively. DSC revealed absence of potential interaction. XRD study revealed presence of amorphous form in nanoparticles. Entrapment efficiency was found to be 83.7 % and drug release was found to be in controlled manner. MTT assay showed low MEC and pharmacokinetic studies showed higher AUC of nanoformulaition than its pristine drug. All these studies revealed that the RES loaded PEG modified core-shell type lipid polymer hybrid nanoparticles can be an alternative tool for chemopreventive and therapeutic application of RES in cancer.

Keywords: trans resveratrol, cancer nanotechnology, long circulating nanoparticles, bioavailability enhancement, core shell nanoparticles, lipid polymer hybrid nanoparticles

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Authors: Mohamed A. Morsy, Azza A. El-Sheikh, Abdulla Y. Al-Taher

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Resveratrol (RES) is a well-known polyphenol antioxidant. We have previously shown that testicular protective effect of RES against the anticancer drug methotrexate (MTX)-induced toxicity involves transporter-mediated mechanisms. Here, we investigated the effect of RES on MTX-induced nephrotoxicity. Rats were administered RES (10 mg/kg/day) for 8 days, with or without a single MTX dose (20 mg/kg i.p.) at day 4 of the experiment. MTX induced nephrotoxicity evident by significantly increase in serum blood urea nitrogen and creatinine compared to control, as well as distortion of kidney microscopic structure. MTX also significantly increased renal nitric oxide level, with induction of inducible nitric oxide synthase expression. MTX also significantly up-regulated fas ligand and caspase 3. Administering RES prior to MTX significantly improved kidney function and microscopic picture, as well as significantly decreased nitrosative and apoptotic markers compared to MTX alone. RES, but not MTX, caused significant increase in expression of breast cancer resistance protein (BCRP), an apical efflux renal transporter that participates in urinary elimination of both MTX and RES. Interestingly, concomitant MTX and RES caused further up-regulation of renal Bcrp compared to RES alone. Using Human BCRP ATPase assay, both RES and MTX exhibited dose-dependent increase in ATPase activity, with Km values of 0.52 ± 0.03 and 30.9 ± 4.2 µM, respectively. Furthermore, combined RES and MTX caused ATPase activity which was significantly less than maximum ATPase activity attained by the positive control; sulfasalazine (12.5 µM). In conclusion, RES exerted nephro-protection against MTX-induced toxicity through anti-nitrosative and anti-apoptotic effects, as well as via up-regulation of renal Bcrp.

Keywords: methotrexate, resveratrol, nephrotoxicity, breast cancer resistance protein

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Authors: Gaoguang Yang, Shan Fu

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Human-machine interface (HMI) intermediate system information to human operators to facilitate human ability to manage and control the system. Well-designed HMI would enhance human ability. An evaluation must be performed to confirm that the designed HMI would enhance but not degrade human ability. However, the prevalent HMI evaluation techniques have difficulties in more thoroughly and accurately evaluating the suitability and fitness of a given HMI for the wide variety of uncertainty contained in both the existing HMI evaluation techniques and the large number of task scenarios. The first limitation should be attributed to the subjective and qualitative analysis characteristics of these evaluation methods, and the second one should be attributed to the cost balance. This study aims to explore the connection between objective HMI characters and ergonomic safety and step forward toward solving these limitations with objective, characterized HMI parameters. A simulation experiment was performed with the time needed for human operators to recognize the HMI information as characterized HMI parameter, and the result showed a strong correlation between the parameter and ergonomic safety level.

Keywords: Human-Machine Interface (HMI), evaluation, objective, characterization, simulation

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