Search results for: recycle service strategy

Authors: Kevin F. Hsu, Alvin Chua, Sarah X. Lin

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As a multilingual society, Singaporean names for different parts of the city have changed over time. Residents included Indigenous Malays, dialect-speakers from China, European settler-colonists, and Tamil-speakers from South India. Each group would name locations in their own languages. Today, as ancestral tongues are increasingly supplanted by English, contemporary Singaporeans’ understanding of once-common place names is disappearing. After demolition or redevelopment, some urban places will only exist in archival records or in human memory. United Nations conferences on the standardization of geographic names have called attention to how place names relate to identity, well-being, and a sense of belonging. The Singapore Place-Naming Project responds to these imperatives by capturing past and present place names through digitizing historical maps, mining archival records, and applying selective crowd-sourcing to trace the evolution of place names throughout the city. The project ensures that both formal and vernacular geographical names remain accessible to historians, city planners, and the public. The project is compiling a gazetteer, a geospatial archive of placenames, with streets, buildings, landmarks, and other points of interest (POI) appearing in the historic maps and planning documents of Singapore, currently held by the National Archives of Singapore, the National Library Board, university departments, and the Urban Redevelopment Authority. To create a spatial layer of information, the project links each place name to either a geo-referenced point, line segment, or polygon, along with the original source material in which the name appears. This record is supplemented by crowd-sourced contributions from civil service officers and heritage specialists, drawing from their collective memory to (1) define geospatial boundaries of historic places that appear in past documents, but maybe unfamiliar to users today, and (2) identify and record vernacular place names not captured in formal planning documents. An intuitive interface allows participants to demarcate feature classes, vernacular phrasings, time periods, and other knowledge related to historical or forgotten spaces. Participants are stratified into age bands and ethnicity to improve representativeness. Future iterations could allow additional public contributions. Names reveal meanings that communities assign to each place. While existing historical maps of Singapore allow users to toggle between present-day and historical raster files, this project goes a step further by adding layers of social understanding and planning documents. Tracking place names illuminates linguistic, cultural, commercial, and demographic shifts in Singapore, in the context of transformations of the urban environment. The project also demonstrates how a moderated, selectively crowd-sourced effort can solicit useful geospatial data at scale, sourced from different generations, and at higher granularity than traditional surveys, while mitigating negative impacts of unmoderated crowd-sourcing. Stakeholder agencies believe the project will achieve several objectives, including Supporting heritage conservation and public education; Safeguarding intangible cultural heritage; Providing historical context for street, place or development-renaming requests; Enhancing place-making with deeper historical knowledge; Facilitating emergency and social services by tagging legal addresses to vernacular place names; Encouraging public engagement with heritage by eliciting multi-stakeholder input.

Keywords: collective memory, crowd-sourced, digital heritage, geospatial, geographical names, linguistic heritage, place-naming, Singapore, Southeast Asia

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Authors: Mohamed Sameer Mughal, Andrew D. Ross, Damian J. Fearon

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Background: The fast-paced changing landscape of UK Higher Education Institution (HEIs) is poised by changes and challenges affecting Middle Managers (MM) in their job roles. MM contribute to the success of HEIs by balancing the equilibrium and pass organization strategies from senior staff towards operationalization directives to junior staff. However, this study showcased from the data analyzed during the semi structured interviews; MM job role is becoming more complex due to changes and challenges creating colossal pressures and workloads in day-to-day working. Current development programmes provisions by Human Resources (HR) departments in such HEIs are not feasible, applicable, and matching the true essence and requirements of MM who suggest that programmes offered by HR are too generic to suit their precise needs and require tailor made espousal to work effectively in their pertinent job roles. Methodologies: This study aims to capture demands of MM Development Needs (DN) by means of a conceptual model as conclusive part of the research that is divided into 2 phases. Phase 1 initiated by carrying out 2 pilot interviews with a retired Emeritus status professor and HR programmes development coordinator. Key themes from the pilot and literature review subsidized into formulation of 22 set of questions (Kvale and Brinkmann) in form of interviewing questionnaire during qualitative data collection. Data strategy and collection consisted of purposeful sampling of 12 semi structured interviews (n=12) lasting approximately an hour for all participants. The MM interviewed were at faculty and departmental levels which included; deans (n=2), head of departments (n=4), subject leaders (n=2), and lastly programme leaders (n=4). Participants recruitment was carried out via emails and snowballing technique. The interviews data was transcribed (verbatim) and managed using Computer Assisted Qualitative Data Analysis using Nvivo ver.11 software. Data was meticulously analyzed using Miles and Huberman inductive approach of positivistic style grounded theory, whereby key themes and categories emerged from the rich data collected. The data was precisely coded and classified into case studies (Robert Yin); with a main case study, sub cases (4 classes of MM) and embedded cases (12 individual MMs). Major Findings: An interim conceptual model emerged from analyzing the data with main concepts that included; key performance indicators (KPI’s), HEI effectiveness and outlook, practices, processes and procedures, support mechanisms, student events, rules, regulations and policies, career progression, reporting/accountability, changes and challenges, and lastly skills and attributes. Conclusion: Dynamic elements affecting MM includes; increase in government pressures, student numbers, irrelevant development programmes, bureaucratic structures, transparency and accountability, organization policies, skills sets… can only be confronted by employing structured development programmes originated by HR that are not provided generically. Future Work: Stage 2 (Quantitative method) of the study plans to validate the interim conceptual model externally through fully completed online survey questionnaire (Bram Oppenheim) from external HEIs (n=150). The total sample targeted is 1500 MM. Author contribution focuses on enhancing management theory and narrow the gap between by HR and MM development programme provision.

Keywords: development needs (DN), higher education institutions (HEIs), human resources (HR), middle managers (MM)

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Authors: Lan Cheng, Harry Qin, Yang Wang

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Background: COVID-19 has induced the largest digital learning experiment in history. There is also emerging research evidence that students have paid a high cost of learning loss from virtual learning. University-wide survey results demonstrate that digital learning remains difficult for students who struggle with learning challenges, isolation, or a lack of resources. Large-scale efforts are therefore increasingly utilized for digital education. To better prepare students in higher education for this grand scientific and technological transformation, STEM education has been prioritized and promoted as a strategic imperative in the ongoing curriculum reform essential for unfinished learning needs and whole-person development. Building upon five key elements identified in the STEM education literature: Problem-based Learning, Community and Belonging, Technology Skills, Personalization of Learning, Connection to the External Community, this case study explores the potential of pedagogical innovation that integrates computational and experimental methodologies to support, enrich, and navigate STEM education. Objectives: The goal of this case study is to create a high-fidelity prototype design for STEM education with knowledge transfer technology that contains a Cooperative Multi-Agent System (CMAS), which has the objectives of (1) conduct assessment to reveal a virtual learning mechanism and establish strategies to facilitate scientific learning engagement, accessibility, and connection within and beyond university setting, (2) explore and validate an interactional co-creation approach embedded in project-based learning activities under the STEM learning context, which is being transformed by both digital technology and student behavior change,(3) formulate and implement the STEM-oriented campaign to guide learning network mapping, mitigate the loss of learning, enhance the learning experience, scale-up inclusive participation. Methods: This study applied a case study strategy and a methodology informed by Social Network Analysis Theory within a cross-disciplinary communication paradigm (students, peers, educators). Knowledge transfer technology is introduced to address learning challenges and to increase the efficiency of Reinforcement Learning (RL) algorithms. A co-creation learning framework was identified and investigated in a context-specific way with a learning analytic tool designed in this study. Findings: The result shows that (1) CMAS-empowered learning support reduced students’ confusion, difficulties, and gaps during problem-solving scenarios while increasing learner capacity empowerment, (2) The co-creation learning phenomenon have examined through the lens of the campaign and reveals that an interactive virtual learning environment fosters students to navigate scientific challenge independently and collaboratively, (3) The deliverables brought from the STEM educational campaign provide a methodological framework both within the context of the curriculum design and external community engagement application. Conclusion: This study brings a holistic and coherent pedagogy to cultivates students’ interest in STEM and develop them a knowledge base to integrate and apply knowledge across different STEM disciplines. Through the co-designing and cross-disciplinary educational content and campaign promotion, findings suggest factors to empower evidence-based learning practice while also piloting and tracking the impact of the scholastic value of co-creation under the dynamic learning environment. The data nested under the knowledge transfer technology situates learners’ scientific journey and could pave the way for theoretical advancement and broader scientific enervators within larger datasets, projects, and communities.

Keywords: co-creation, cross-disciplinary, knowledge transfer, STEM education, social network analysis

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Authors: Chiu-Yin Leung

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This research investigates a complex assemblage among indigenous identities, socio-political organization and national apparatus in the border landscape of post-colonial Hong Kong. This former British colony had designated a transient mode of governance in its New Territories and particularly the northernmost borderland in 1951-2012. With a discriminated system of land provisions for the indigenous villagers, the place has been inherited with distinctive village-based culture, historic monuments and agrarian practices until its sovereignty return into the People’s Republic of China. In its latest development imperatives by the national strategic planning, the frontier area of Hong Kong has been identified as a strategy site for regional economic integration in South China, with cross-border projects of innovation and technology zones, mega-transport infrastructure and inter-jurisdictional arrangement. Contemporary literature theorizes borders as the material and discursive production of territoriality, which manifest in state apparatus and the daily lives of its citizens and condense in the contested articulations of power, security and citizenship. Drawing on the concept of assemblage, this paper attempts to tract how the border regime and infrastructure in Hong Kong as a city are deeply ingrained in the everyday lived spaces of the local communities but also the changing urban and regional strategies across different longitudinal moments. Through an intensive ethnographic fieldwork among the borderland villages since 2008 and the extensive analysis of colonial archives, new development plans and spatial planning frameworks, the author navigates the genealogy of the border landscape in Ta Kwu Ling frontier area and its implications as the milieu for new state space, covering heterogeneous fields particularly in indigenous rights, heritage preservation, rural sustainability and regional economy. Empirical evidence suggests an apparent bias towards indigenous power and colonial representation in classifying landscape values and conserving historical monuments. Squatter and farm tenants are often deprived of property rights, statutory participation and livelihood option in the planning process. The postcolonial bureaucracies have great difficulties in mobilizing resources to catch up with the swift, political-first approach of the mainland counterparts. Meanwhile, the cultural heritage, lineage network and memory landscape are not protected altogether with any holistic view or collaborative effort across the border. The enactment of land resumption and compensation scheme is furthermore disturbed by lineage-based customary law, technocratic bureaucracy, intra-community conflicts and multi-scalar political mobilization. As many traces of colonial misfortune and tyranny have been whitewashed without proper management, the author argues that postcolonial justice is yet reconciled in this fragmented border landscape. The assemblage of border in mainstream representation has tended to oversimplify local struggles as a collective mist and setup a wider production of schizophrenia experiences in the discussion of further economic integration among Hong Kong and other mainland cities in the Pearl River Delta Region. The research is expected to shed new light on the theorizing of border regions and postcolonialism beyond Eurocentric perspectives. In reassembling the borderland experiences with other arrays in state governance, village organization and indigenous identities, the author also suggests an alternative epistemology in reconciling socio-spatial differences and opening up imaginaries for positive interventions.

Keywords: heritage conservation, indigenous communities, post-colonial borderland, regional development, rural sustainability

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Authors: Humaira Maheen, Elizabeth Hoban, Catherine Bennette

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Background: Globally, role of Community Health Workers (CHW) as front line disaster health work force is underutilized. Developing countries which are at risk of natural disasters or humanitarian emergencies should lay down effective strategies especially to ensure adequate access to maternity care during crisis situation by using CHW as they are local, trained, and most of them possess a good relationship with the community. The Minimum Initial Service Package (MISP) is a set of universal guidelines that addresses women’s reproductive health needs during the first phase of an emergency. According to the MISP, pregnant women should have access to a skilled birth attendant and adequate transportation arrangements so they can access a maternity care facility. Pakistan is one of the few countries which has been severely affected by a number of natural disaster as well as humanitarian emergencies in last decade. Pakistan has a young and structured National Disaster Management System in place, where District Authorities play a vital role in disaster management. The District Health Department develops the contingency health plan for an emergency situation and implements it under the existing district health human resources (health workers and medical staff at the health facility) and infrastructure (health care facilities). Methods: A mixed methods study was conducted in rural villages of Sindh adjacent to the river Indus, and included in-depth interviews with 15 women who gave birth during the floods, structured interviews with 668 women who were pregnant during 2010-2014, and in-depth interviews with 25 community health workers (CHW) and 30 key informants. Results: Women said that giving birth in the relief camps during the floods was one of the most challenging times of their life. The district health department didn’t make transportation arrangement for labouring women from relief camp to the nearest health care facility. As a result 91.2% women gave birth in temporary shelters with the help of a traditional birth attendant (Dai) with no clean physical space available to birth. Of the 332 women who were pregnant at the time of the floods, 26 had adverse birth outcomes; 10 had miscarriages, 14 had stillbirths and there were four neonatal deaths. Conclusion: The district health department was not able to provide access to adequate maternity care during according to the international standard during the floods in 2011. We propose a model where CHWs will be used as frontline maternity care providers during any emergency or disaster situations in Pakistan. A separate "birthing station" should be mandatory in all district relief camps, managed by CHWs. Community midwives (CMW) would and the Lady Health Workers (LHW) would provide antenatal and postnatal care alongside, vaccination for pregnant women, neonates and children under five. There must be an ambulance facility for emergency obstetric cases and all district health facilities should have at least two medical staff identified and trained for emergency obstetric management. The District Health Department must provide clean birthing kits and regular and emergency contraceptives in the relief camps. Methods: A mixed methods study was conducted in rural villages of Sindh adjacent to the river Indus, and included in-depth interviews with 15 women who gave birth during the floods, structured interviews with 668 women who were pregnant during 2010-2014, and in-depth interviews with 25 community health workers (CHW) and 30 key informants. Results: Women said that giving birth in the relief camps during the floods was one of the most challenging times of their life. Nearly 91.2% women gave birth in temporary shelters with the help of a traditional birth attendant (Dai) with no clean physical space available to birth, and the health camp was mostly accessed by men and always overcrowded. There was no obstetric trained medical staff in the health camps or transportation provided to take women with complications to the nearest health facility. The rate of adverse outcome following disaster was 22.2% (95% CI: 8.62% – 42.2%) amongst 27 women who did not evacuate as compare to 7.91% (95% CI: 5.03% – 11.8%) among 278 women who lived in relief camp study participants. There were 27 women who evacuated on pre-flood warning and had 0% rate of adverse outcome. Conclusion: We propose a model where CHWs will be used as frontline maternity care providers during any emergency or disaster situations in Pakistan. A separate "birthing station" should be mandatory in all district relief camps, managed by CHWs. Community midwives (CMW) would and the Lady Health Workers (LHW) would provide antenatal and postnatal care alongside, vaccination for pregnant women, neonates and children under five. There must be an ambulance facility for emergency obstetric cases and all district health facilities should have at least two medical staff identified and trained for emergency obstetric management. The District Health Department must provide clean birthing kits and regular and emergency contraceptives in the relief camps.

Keywords: natural disaster, maternity care model, rural, Pakistan, community health workers

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Authors: Zhi-Zhong Chen, Jun-Hao Lu, Jr., Shih-Ying Chueh

Abstract:

Based on Unified Theory of Acceptance and Use of Technology (UTAUT), the study investigates people’s intention on using smart phones. The study additionally incorporates two new variables: 'self-efficacy' and 'attitude toward using'. Samples are collected by questionnaire survey, in which 240 are valid. After Correlation Analysis, Reliability Test, ANOVA, t-test and Multiple Regression Analysis, the study finds that social impact and self-efficacy have positive effect on use intentions, and the use intentions also have positive effect on use behavior.

Keywords: [1] Ajzen & Fishbein (1975), “Belief, attitude, intention and behavior: An introduction to theory and research”, Reading MA: Addison-Wesley. [2] Bandura (1977) Self-efficacy: toward a unifying theory of behavioural change. Psychological Review , 84, 191–215. [3] Bandura( 1986) A. Bandura, Social foundations of though and action, Prentice-Hall. Englewood Cliffs. [4] Ching-Hui Huang (2005). The effect of Regular Exercise on Elderly Optimism: The Self-efficacy and Theory of Reasoned Action Perspectives.(Master's dissertation, National Taiwan Sport University, 2005).National Digital Library of Theses and Dissertations in Taiwan。 [5] Chun-Mo Wu (2007).The Effects of Perceived Risk and Service Quality on Purchase Intention - an Example of Taipei City Long-Term Care Facilities. (Master's dissertation, Ming Chuan University, 2007).National Digital Library of Theses and Dissertations in Taiwan. [6] Compeau, D.R., and Higgins, C.A., (1995) “Application of social cognitive theory to training for computer skills.”, Information Systems Research, 6(2), pp.118-143. [7] computer-self-efficacy and mediators of the efficacy-performance relationship. International Journal of Human-Computer Studies, 62, 737-758. [8] Davis et al(1989), “User acceptance of computer technology: A comparison of two theoretical models ”, Management Science, 35(8), p.982-1003. [9] Davis et al(1989), “User acceptance of computer technology:A comparison of two theoretical models ”, Management Science, 35(8), p.982-1003. [10] Davis, F.D. (1989). Perceived Usefulness, Perceived Ease of Use and User Acceptance of Information Technology. MIS Quarterly, 13(3), 319-340。 [11] Davis. (1989). Perceived Usefulness, Perceived Ease of Use, and User Acceptance of Information Technology. MIS Quarterly, 13(3), 319–340. doi:10.2307/249008 [12] Johnson, R. D. (2005). An empirical investigation of sources of application-specific [13] Mei-yin Hsu (2010).The Study on Attitude and Satisfaction of Electronic Documents System for Administrators of Elementary Schools in Changhua County.(Master's dissertation , Feng Chia University, 2010).National Digital Library of Theses and Dissertations in Taiwan. [14] Ming-Chun Hsieh (2010). Research on Parents’ Attitudes Toward Electronic Toys： The case of Taichung City.(Master's dissertation, Chaoyang University of Technology，2010).National Digital Library of Theses and Dissertations in Taiwan. [15] Moon and Kim（2001）. Extending the TAM for a World-Wide-Web context, Information and Management, v.38 n.4, p.217-230. [16] Shang-Yi Hu (2010).The Impacts of Knowledge Management on Customer Relationship Management – Enterprise Characteristicsand Corporate Governance as a Moderator.(Master's dissertation, Leader University, 2010)。National Digital Library of Theses and Dissertations in Taiwan. [17] Sheng-Yi Hung (2013, September10).Worldwide sale of smartphones to hit one billion IDC：Android dominate the market. ETtoday. Retrieved data form the available protocol:2013/10/3. [18] Thompson, R.L., Higgins, C.A., and Howell, J.M.(1991), “Personal Computing: Toward a Conceptual Model of Utilization”, MIS Quarterly(15:1), pp. 125-143. [19] Venkatesh, V., M.G. Morris, G.B. Davis, and F. D. Davis (2003), “User acceptance of information technology: Toward a unified view, ” MIS Quarterly, 27, No. 3, pp.425-478. [20] Vijayasarathy, L. R. (2004), Predicting Consumer Intentions to Use On-Line Shopping： The Case for an Augmented Technology Acceptance Model, Information and Management, Vol.41, No.6, pp.747-762. [21] Wikipedia - smartphone (http://zh.wikipedia.org/zh-tw/%E6%99%BA%E8%83%BD%E6%89%8B%E6%9C%BA)。 [22] Wu-Minsan (2008).The impacts of self-efficacy, social support on work adjustment with hearing impaired. (Master's dissertation, Southern Taiwan University of Science and Technology, 2008).National Digital Library of Theses and Dissertations in Taiwan. [23] Yu-min Lin (2006). The Influence of Business Employee’s MSN Self-efficacy On Instant Messaging Usage Behavior and Communicaiton Satisfaction.(Master's dissertation, National Taiwan University of Science and Technology, 2006).National Digital Library of Theses and Dissertations in Taiwan.

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Authors: Hosein Maghsoudi

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Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.

Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9

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Authors: Ziyad S. Haidar

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Background: Saliva plays a major role in maintaining oral and dental health (consequently, general health and well-being). Where it normally bathes the oral cavity and acts as a clearing agent. This becomes more apparent when the amount and quality of salivare significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the fifth most common malignancy worldwide, during which the salivary glands are included within the radiation field or zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely because they become malnourished and experience a significant decrease in their quality of life. Accordingly, the development of an alternative treatment to restore or regenerate damaged salivary gland tissue is eagerly awaited. Likewise, the formulation of a radioprotection modality and early damage prevention strategy is also highly desirable. Objectives: To assess the pre-clinical radio-protective effect as well as the reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned in this experimental work for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs (in solution and powder formats), followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy (revised from our previous 15Gy model) was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: saliva, head and neck cancer, nanotechnology, controlled drug delivery, xerostomia, mucositis, biopolymers, innovation

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