Search results for: transport damage

Authors: A. Chandra, M. Arthur, L. Mize, A. Pomeroy-Stevens

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Background: Lower and middle-income countries (LMICs) in Asia face rapid urbanization resulting in both economic opportunities (the urban advantage) and emerging health challenges. Urban health risks are magnified in informal settlements and include infectious disease outbreaks, inadequate access to health services, and poor air quality. Over the coming years, urban spaces in Asia will face accelerating public health risks related to migration, climate change, and environmental health. These challenges are complex and require multi-sectoral and multi-stakeholder solutions. The Building Health Cities (BHC) program is funded by the United States Agency for International Development (USAID) to work with smart city initiatives in the Asia region. BHC approaches urban health challenges by addressing policies, planning, and services through a health equity lens, with a particular focus on informal settlements and migrant communities. The program works to develop data-driven decision-making, build inclusivity through stakeholder engagement, and facilitate the uptake of appropriate technology. Methodology: The BHC program has partnered with the smart city initiatives of Indore in India, Makassar in Indonesia, and Da Nang in Vietnam. Implementing partners support municipalities to improve health delivery and equity using two key approaches: political economy analysis and participatory systems mapping. Political economy analyses evaluate barriers to collective action, including corruption, security, accountability, and incentives. Systems mapping evaluates community health challenges using a cross-sectoral approach, analyzing the impact of economic, environmental, transport, security, health system, and built environment factors. The mapping exercise draws on the experience and expertise of a diverse cohort of stakeholders, including government officials, municipal service providers, and civil society organizations. Results: Systems mapping and political economy analyses identified significant barriers for health care in migrant populations. In Makassar, migrants are unable to obtain the necessary card that entitles them to subsidized health services. This finding is being used to engage with municipal governments to mitigate the barriers that limit migrant enrollment in the public social health insurance scheme. In Indore, the project identified poor drainage of storm and wastewater in migrant settlements as a cause of poor health. Unsafe and inadequate infrastructure placed residents of these settlements at risk for both waterborne diseases and injuries. The program also evaluated the capacity of urban primary health centers serving migrant communities, identifying challenges related to their hours of service and shortages of health workers. In Da Nang, the systems mapping process has only recently begun, with the formal partnership launched in December 2019. Conclusion: This paper explores lessons learned from BHC’s systems mapping, political economy analyses, and stakeholder engagement approaches. The paper shares progress related to the health of migrants in informal settlements. Case studies feature barriers identified and mitigating steps, including governance actions, taken by local stakeholders in partner cities. The paper includes an update on ongoing progress from Indore and Makassar and experience from the first six months of program implementation from Da Nang.

Keywords: informal settlements, migration, stakeholder engagement mapping, urban health

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Authors: Yimer Mohammed Assen, Abiyot Legesse Kura, Engida Esyas Dube, Asebe Regassa Debelo, Girma Kelboro Mensuro, Lete Bekele Gure

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Climate change has posed severe threats to many cultural landscapes of UNESCO world heritage sites recently. The UNESCO State of Conservation (SOC) reports categorized flooding, temperature increment, and drought as threats to cultural landscapes. This study aimed to examine variations and trends of rainfall and temperature extreme events and their threats to the UNESCO-designated Konso Cultural Landscape in southern Ethiopia. The study used dense merged satellite-gauge station rainfall data (1981-2020) with spatial resolution of 4km by 4km and observed maximum and minimum temperature data (1987-2020). Qualitative data were also gathered from cultural leaders, local administrators, and religious leaders using structured interview checklists. The spatial patterns, coefficient of variation, standardized anomalies, trends, and magnitude of change of rainfall and temperature extreme events both at annual and seasonal levels were computed using the Mann-Kendall trend test and Sen’s slope estimator under the CDT package. The standard precipitation index (SPI) was also used to calculate drought severity, frequency, and trend maps. The data gathered from key informant interviews and focus group discussions were coded and analyzed thematically to complement statistical findings. Thematic areas that explain the impacts of extreme events on the cultural landscape were chosen for coding. The thematic analysis was conducted using Nvivo software. The findings revealed that rainfall was highly variable and unpredictable, resulting in extreme drought and flood. There were significant (P<0.05) increasing trends of heavy rainfall (R10mm and R20mm) and the total amount of rain on wet days (PRCPTOT), which might have resulted in flooding. The study also confirmed that absolute temperature extreme indices (TXx, TXn, and TNx) and the percentile-based temperature extreme indices (TX90p, TN90p, TX10p, and TN10P) showed significant (P<0.05) increasing trends which are signals for warming of the study area. The results revealed that the frequency as well as the severity of drought at 3-months (katana/hageya seasons) was more pronounced than the 12-months (annual) time scale. The highest number of droughts in 100 years is projected at a 3-months timescale across the study area. The findings also showed that frequent drought has led to loss of grasses which are used for making traditional individual houses and multipurpose communal houses (pafta), food insecurity, migration, loss of biodiversity, and commodification of stones from terrace. On the other hand, the increasing trends of rainfall extreme indices resulted in destruction of terraces, soil erosion, loss of life and damage of properties. The study shows that a persistent decline in farmland productivity, due to erratic and extreme rainfall and frequent drought occurrences, forced the local people to participate in non-farm activities and retreat from daily preservation and management of their landscape. Overall, the increasing rainfall and temperature extremes coupled with prevalence of drought are thought to have an impact on the sustainability of cultural landscape through disrupting the ecosystem services and livelihood of the community. Therefore, more localized adaptation and mitigation strategies to the changing climate are needed to maintain the sustainability of Konso cultural landscapes as a global cultural treasure and to strengthen the resilience of smallholder farmers.

Keywords: adaptation, cultural landscape, drought, extremes indices

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Authors: Essam Gooda, Chadi Abdallah, Hamdi Seif, Safaa Baydoun, Rouya Hdeib, Hilal Obeid

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Floods are common natural disaster occurring in semi-arid regions in Lebanon. This results in damage to human life and deterioration of environment. Despite their destructive nature and their immense impact on the socio-economy of the region, flash floods have not received adequate attention from policy and decision makers. This is mainly because of poor understanding of the processes involved and measures needed to manage the problem. The current understanding of flash floods remains at the level of general concepts; most policy makers have yet to recognize that flash floods are distinctly different from normal riverine floods in term of causes, propagation, intensity, impacts, predictability, and management. Flash floods are generally not investigated as a separate class of event but are rather reported as part of the overall seasonal flood situation. As a result, Lebanon generally lacks policies, strategies, and plans relating specifically to flash floods. Main objective of this research is to improve flash flood prediction by providing new knowledge and better understanding of the hydrological processes governing flash floods in the East Catchments of El Assi River. This includes developing rainstorm time distribution curves that are unique for this type of study region; analyzing, investigating, and developing a relationship between arid watershed characteristics (including urbanization) and nearby villages flow flood frequency in Ras Baalbeck and Fekha. This paper discusses different levels of integration approach¬es between GIS and hydrological models (HEC-HMS & HEC-RAS) and presents a case study, in which all the tasks of creating model input, editing data, running the model, and displaying output results. The study area corresponds to the East Basin (Ras Baalbeck & Fakeha), comprising nearly 350 km2 and situated in the Bekaa Valley of Lebanon. The case study presented in this paper has a database which is derived from Lebanese Army topographic maps for this region. Using ArcMap to digitizing the contour lines, streams & other features from the topographic maps. The digital elevation model grid (DEM) is derived for the study area. The next steps in this research are to incorporate rainfall time series data from Arseal, Fekha and Deir El Ahmar stations to build a hydrologic data model within a GIS environment and to combine ArcGIS/ArcMap, HEC-HMS & HEC-RAS models, in order to produce a spatial-temporal model for floodplain analysis at a regional scale. In this study, HEC-HMS and SCS methods were chosen to build the hydrologic model of the watershed. The model then calibrated using flood event that occurred between 7th & 9th of May 2014 which considered exceptionally extreme because of the length of time the flows lasted (15 hours) and the fact that it covered both the watershed of Aarsal and Ras Baalbeck. The strongest reported flood in recent times lasted for only 7 hours covering only one watershed. The calibrated hydrologic model is then used to build the hydraulic model & assessing of flood hazards maps for the region. HEC-RAS Model is used in this issue & field trips were done for the catchments in order to calibrated both Hydrologic and Hydraulic models. The presented models are a kind of flexible procedures for an ungaged watershed. For some storm events it delivers good results, while for others, no parameter vectors can be found. In order to have a general methodology based on these ideas, further calibration and compromising of results on the dependence of many flood events parameters and catchment properties is required.

Keywords: flood risk management, flash flood, semi arid region, El Assi River, hazard maps

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Authors: Volker Wannack

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Regional, national, and international strategies focusing on hydrogen (H₂) and blockchain are driving significant advancements in hydrogen and blockchain technology worldwide. These strategies lay the foundation for the groundbreaking "Blockchain Based Hydrogen Market (BBH₂)" project. The primary goal of this project is to develop a functional Blockchain Minimum Viable Product (B-MVP) for the hydrogen market. The B-MVP will leverage blockchain as an enabling technology with a common database and platform, facilitating secure and automated transactions through smart contracts. This innovation will revolutionize logistics, trading, and transactions within the hydrogen market. The B-MVP has transformative potential across various sectors. It benefits renewable energy producers, surplus energy-based hydrogen producers, hydrogen transport and distribution grid operators, and hydrogen consumers. By implementing standardized, automated, and tamper-proof processes, the B-MVP enhances cost efficiency and enables transparent and traceable transactions. Its key objective is to establish the verifiable integrity of climate-friendly "green" hydrogen by tracing its supply chain from renewable energy producers to end users. This emphasis on transparency and accountability promotes economic, ecological, and social sustainability while fostering a secure and transparent market environment. A notable feature of the B-MVP is its cross-border operability, eliminating the need for country-specific data storage and expanding its global applicability. This flexibility not only broadens its reach but also creates opportunities for long-term job creation through the establishment of a dedicated blockchain operating company. By attracting skilled workers and supporting their training, the B-MVP strengthens the workforce in the growing hydrogen sector. Moreover, it drives the emergence of innovative business models that attract additional company establishments and startups and contributes to long-term job creation. For instance, data evaluation can be utilized to develop customized tariffs and provide demand-oriented network capacities to producers and network operators, benefitting redistributors and end customers with tamper-proof pricing options. The B-MVP not only brings technological and economic advancements but also enhances the visibility of national and international standard-setting efforts. Regions implementing the B-MVP become pioneers in climate-friendly, sustainable, and forward-thinking practices, generating interest beyond their geographic boundaries. Additionally, the B-MVP serves as a catalyst for research and development, facilitating knowledge transfer between universities and companies. This collaborative environment fosters scientific progress, aligns with strategic innovation management, and cultivates an innovation culture within the hydrogen market. Through the integration of blockchain and hydrogen technologies, the B-MVP promotes holistic innovation and contributes to a sustainable future in the hydrogen industry. The implementation process involves evaluating and mapping suitable blockchain technology and architecture, developing and implementing the blockchain, smart contracts, and depositing certificates of origin. It also includes creating interfaces to existing systems such as nomination, portfolio management, trading, and billing systems, testing the scalability of the B-MVP to other markets and user groups, developing data formats for process-relevant data exchange, and conducting field studies to validate the B-MVP. BBH₂ is part of the "Technology Offensive Hydrogen" funding call within the research funding of the Federal Ministry of Economics and Climate Protection in the 7th Energy Research Programme of the Federal Government.

Keywords: hydrogen, blockchain, sustainability, innovation, structural change

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Authors: Stephan Treuke

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The paper analyses the neighbourhood effects on the economic mobility of the inhabitants of three segregated communities of Salvador (Brazil), in other words, the socio-economic advantages and disadvantages affecting the lives of poor people due to their embeddedness in specific socio-residential contexts. Recent studies performed in Brazilian metropolis have concentrated on the structural dimensions of negative externalities in order to explain neighbourhood-level variations in a field of different phenomena (delinquency, violence, access to the labour market and education) in spatial isolated and socially homogeneous slum areas (favelas). However, major disagreement remains whether the contiguity between residents of poor neighbourhoods and higher-class condominio-dwellers provides structures of opportunities or whether it fosters socio-spatial stigmatization. Based on a set of interviews, investigating the variability of interpersonal networks and their activation in the struggle for economic inclusion, the study confirms that the proximity of Nordeste de Amaralina to middle-/upper-class communities affects positively the access to labour opportunities. Nevertheless, residential stigmatization, as well as structures of social segmentation, annihilate these potentials. The lack of exposition to individuals and groups extrapolating from the favela’s social, educational and cultural context restricts the structures of opportunities to local level. Therefore, residents´ interpersonal networks reveal a high degree of redundancy and localism, based on bonding ties connecting family and neighbourhood members. The resilience of segregational structures in Plataforma contributes to the naturalization of social distance patters. It’s embeddedness in a socially homogeneous residential area (Subúrbio Ferroviário), growing informally and beyond official urban politics, encourages the construction of isotopic patterns of sociability, sharing the same values, social preferences, perspectives and behaviour models. Whereas it’s spatial isolation correlates with the scarcity of economic opportunities, the social heterogeneity of Fazenda Grande II interviewees and the socialising effects of public institutions mitigate the negative repercussions of segregation. The networks’ composition admits a higher degree of heterophilia and a greater proportion of bridging ties accounting for the access to broader information actives and facilitating economic mobility. The variability observed within the three different scenarios urges to reflect about the responsability of urban politics when it comes to the prevention or consolidation of the social segregation process in Salvador. Instead of promoting the local development of the favela Plataforma, public housing programs priorize technocratic habitational solutions without providing the residents’ socio-economic integration. The impact of negative externalities related to the homogeneously poor neighbourhood is potencialized in peripheral areas, turning its’ inhabitants socially invisible, thus being isolated from other social groups. The example of Nordeste de Amaralina portrays the failing interest of urban politics to bridge the social distances structuring the brazilian society’s rigid stratification model, founded on mecanisms of segmentation (unequal access to labour market and education system, public transport, social security and law protection) and generating permanent conflicts between the two socioeconomically distant groups living in geographic contiguity. Finally, in the case of Fazenda Grande II, the public investments in both housing projects and complementary infrastructure (e.g. schools, hospitals, community center, police stations, recreation areas) contributes to the residents’ socio-economic inclusion.

Keywords: economic mobility, neighborhood effects, Salvador, segregation

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Authors: Manavjit Singh Dhindsa, Ursula Das, Kshirasagar Naik, Marzia Zaman, Richard Purcell, Srinivas Sampalli, Abdul Mutakabbir, Chung-Horng Lung, Thambirajah Ravichandran

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These days, wildland fires, also known as forest fires, are more prevalent than ever. Wildfires have major repercussions that affect ecosystems, communities, and the environment in several ways. Wildfires lead to habitat destruction and biodiversity loss, affecting ecosystems and causing soil erosion. They also contribute to poor air quality by releasing smoke and pollutants that pose health risks, especially for individuals with respiratory conditions. Wildfires can damage infrastructure, disrupt communities, and cause economic losses. The economic impact of firefighting efforts, combined with their direct effects on forestry and agriculture, causes significant financial difficulties for the areas impacted. This research explores different forest fire spread models and presents a comprehensive review of various techniques and methodologies used in the field. A forest fire spread model is a computational or mathematical representation that is used to simulate and predict the behavior of a forest fire. By applying scientific concepts and data from empirical studies, these models attempt to capture the intricate dynamics of how a fire spreads, taking into consideration a variety of factors like weather patterns, topography, fuel types, and environmental conditions. These models assist authorities in understanding and forecasting the potential trajectory and intensity of a wildfire. Emphasizing the need for a comprehensive understanding of wildfire dynamics, this research explores the approaches, assumptions, and findings derived from various models. By using a comparison approach, a critical analysis is provided by identifying patterns, strengths, and weaknesses among these models. The purpose of the survey is to further wildfire research and management techniques. Decision-makers, researchers, and practitioners can benefit from the useful insights that are provided by synthesizing established information. Fire spread models provide insights into potential fire behavior, facilitating authorities to make informed decisions about evacuation activities, allocating resources for fire-fighting efforts, and planning for preventive actions. Wildfire spread models are also useful in post-wildfire mitigation strategies as they help in assessing the fire's severity, determining high-risk regions for post-fire dangers, and forecasting soil erosion trends. The analysis highlights the importance of customized modeling approaches for various circumstances and promotes our understanding of the way forest fires spread. Some of the known models in this field are Rothermel’s wildland fuel model, FARSITE, WRF-SFIRE, FIRETEC, FlamMap, FSPro, cellular automata model, and others. The key characteristics that these models consider include weather (includes factors such as wind speed and direction), topography (includes factors like landscape elevation), and fuel availability (includes factors like types of vegetation) among other factors. The models discussed are physics-based, data-driven, or hybrid models, also utilizing ML techniques like attention-based neural networks to enhance the performance of the model. In order to lessen the destructive effects of forest fires, this initiative aims to promote the development of more precise prediction tools and effective management techniques. The survey expands its scope to address the practical needs of numerous stakeholders. Access to enhanced early warning systems enables decision-makers to take prompt action. Emergency responders benefit from improved resource allocation strategies, strengthening the efficacy of firefighting efforts.

Keywords: artificial intelligence, deep learning, forest fire management, fire risk assessment, fire simulation, machine learning, remote sensing, wildfire modeling

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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: Ziyad S. Haidar

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Background: Saliva plays a major role in maintaining oral, dental, and general health and well-being; where it normally bathes the oral cavity acting as a clearing agent. This becomes more apparent when the amount and quality of saliva are 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 5th most common malignancy worldwide, during which the salivary glands are included within the radiation field/zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely as they become malnourished and experience a significant decrease in their QoL. Accordingly, the formulation of a radio-protection/-prevention modality and development of an alternative Rx to restore damaged salivary gland tissue is eagerly awaited and highly desirable. Objectives: Assess the pre-clinical radio-protective effect and reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned 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, 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 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: cancer, head and neck, oncology, drug development, drug delivery systems, nanotechnology, nanoncology

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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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