Search results for: iodinated contrast agents
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Search results for: iodinated contrast agents

14 A Systematic Review Of Literature On The Importance Of Cultural Humility In Providing Optimal Palliative Care For All Persons

Authors: Roseanne Sharon Borromeo, Mariana Carvalho, Mariia Karizhenskaia

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Healthcare providers need to comprehend cultural diversity for optimal patient-centered care, especially near the end of life. Although a universal method for navigating cultural differences would be ideal, culture’s high complexity makes this strategy impossible. Adding cultural humility, a process of self-reflection to understand personal and systemic biases and humbly acknowledging oneself as a learner when it comes to understanding another's experience leads to a meaningful process in palliative care generating respectful, honest, and trustworthy relationships. This study is a systematic review of the literature on cultural humility in palliative care research and best practices. Race, religion, language, values, and beliefs can affect an individual’s access to palliative care, underscoring the importance of culture in palliative care. Cultural influences affect end-of-life care perceptions, impacting bereavement rituals, decision-making, and attitudes toward death. Cultural factors affecting the delivery of care identified in a scoping review of Canadian literature include cultural competency, cultural sensitivity, and cultural accessibility. As the different parts of the world become exponentially diverse and multicultural, healthcare providers have been encouraged to give culturally competent care at the bedside. Therefore, many organizations have made cultural competence training required to expose professionals to the special needs and vulnerability of diverse populations. Cultural competence is easily standardized, taught, and implemented; however, this theoretically finite form of knowledge can dangerously lead to false assumptions or stereotyping, generating poor communication, loss of bonds and trust, and poor healthcare provider-patient relationship. In contrast, Cultural humility is a dynamic process that includes self-reflection, personal critique, and growth, allowing healthcare providers to respond to these differences with an open mind, curiosity, and awareness that one is never truly a “cultural” expert and requires life-long learning to overcome common biases and ingrained societal influences. Cultural humility concepts include self-awareness and power imbalances. While being culturally competent requires being skilled and knowledgeable in one’s culture, being culturally humble involves the sometimes-uncomfortable position of healthcare providers as students of the patient. Incorporating cultural humility emphasizes the need to approach end-of-life care with openness and responsiveness to various cultural perspectives. Thus, healthcare workers need to embrace lifelong learning in individual beliefs and values on suffering, death, and dying. There have been different approaches to this as well. Some adopt strategies for cultural humility, addressing conflicts and challenges through relational and health system approaches. In practice and research, clinicians and researchers must embrace cultural humility to advance palliative care practices, using qualitative methods to capture culturally nuanced experiences. Cultural diversity significantly impacts patient-centered care, particularly in end-of-life contexts. Cultural factors also shape end-of-life perceptions, impacting rituals, decision-making, and attitudes toward death. Cultural humility encourages openness and acknowledges the limitations of expertise in one’s culture. A consistent self-awareness and a desire to understand patients’ beliefs drive the practice of cultural humility. This dynamic process requires practitioners to learn continuously, fostering empathy and understanding. Cultural humility enhances palliative care, ensuring it resonates genuinely across cultural backgrounds and enriches patient-provider interactions.

Keywords: cultural competency, cultural diversity, cultural humility, palliative care, self-awareness

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13 A Case Study on Utility of 18FDG-PET/CT Scan in Identifying Active Extra Lymph Nodes and Staging of Breast Cancer

Authors: Farid Risheq, M. Zaid Alrisheq, Shuaa Al-Sadoon, Karim Al-Faqih, Mays Abdulazeez

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Breast cancer is the most frequently diagnosed cancer worldwide, and a common cause of death among women. Various conventional anatomical imaging tools are utilized for diagnosis, histological assessment and TNM (Tumor, Node, Metastases) staging of breast cancer. Biopsy of sentinel lymph node is becoming an alternative to the axillary lymph node dissection. Advances in 18-Fluoro-Deoxi-Glucose Positron Emission Tomography/Computed Tomography (18FDG-PET/CT) imaging have facilitated breast cancer diagnosis utilizing biological trapping of 18FDG inside lesion cells, expressed as Standardized Uptake Value (SUVmax). Objective: To present the utility of 18FDG uptake PET/CT scans in detecting active extra lymph nodes and distant occult metastases for breast cancer staging. Subjects and Methods: Four female patients were presented with initially classified TNM stages of breast cancer based on conventional anatomical diagnostic techniques. 18FDG-PET/CT scans were performed one hour post 18FDG intra-venous injection of (300-370) MBq, and (7-8) bed/130sec. Transverse, sagittal, and coronal views; fused PET/CT and MIP modality were reconstructed for each patient. Results: A total of twenty four lesions in breast, extended lesions to lung, liver, bone and active extra lymph nodes were detected among patients. The initial TNM stage was significantly changed post 18FDG-PET/CT scan for each patient, as follows: Patient-1: Initial TNM-stage: T1N1M0-(stage I). Finding: Two lesions in right breast (3.2cm2, SUVmax=10.2), (1.8cm2, SUVmax=6.7), associated with metastases to two right axillary lymph nodes. Final TNM-stage: T1N2M0-(stage II). Patient-2: Initial TNM-stage: T2N2M0-(stage III). Finding: Right breast lesion (6.1cm2, SUVmax=15.2), associated with metastases to right internal mammary lymph node, two right axillary lymph nodes, and sclerotic lesions in right scapula. Final TNM-stage: T2N3M1-(stage IV). Patient-3: Initial TNM-stage: T2N0M1-(stage III). Finding: Left breast lesion (11.1cm2, SUVmax=18.8), associated with metastases to two lymph nodes in left hilum, and three lesions in both lungs. Final TNM-stage: T2N2M1-(stage IV). Patient-4: Initial TNM-stage: T4N1M1-(stage III). Finding: Four lesions in upper outer quadrant area of right breast (largest: 12.7cm2, SUVmax=18.6), in addition to one lesion in left breast (4.8cm2, SUVmax=7.1), associated with metastases to multiple lesions in liver (largest: 11.4cm2, SUV=8.0), and two bony-lytic lesions in left scapula and cervicle-1. No evidence of regional or distant lymph node involvement. Final TNM-stage: T4N0M2-(stage IV). Conclusions: Our results demonstrated that 18FDG-PET/CT scans had significantly changed the TNM stages of breast cancer patients. While the T factor was unchanged, N and M factors showed significant variations. A single session of PET/CT scan was effective in detecting active extra lymph nodes and distant occult metastases, which were not identified by conventional diagnostic techniques, and might advantageously replace bone scan, and contrast enhanced CT of chest, abdomen and pelvis. Applying 18FDG-PET/CT scan early in the investigation, might shorten diagnosis time, helps deciding adequate treatment protocol, and could improve patients’ quality of life and survival. Trapping of 18FDG in malignant lesion cells, after a PET/CT scan, increases the retention index (RI%) for a considerable time, which might help localize sentinel lymph node for biopsy using a hand held gamma probe detector. Future work is required to demonstrate its utility.

Keywords: axillary lymph nodes, breast cancer staging, fluorodeoxyglucose positron emission tomography/computed tomography, lymph nodes

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12 Drug Reaction with Eosinophilia and Systemic Symptoms (Dress) Syndrome Presenting as Multi-Organ Failure

Authors: Keshari Shrestha, Philip Vatterott

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Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal drug-related syndrome. DRESS classically presents with a diffuse maculopapular rash, fevers, and eosinophilia more than three weeks after drug exposure. DRESS can present with multi-organ involvement, with liver damage being the most common and severe. Pulmonary involvement is a less common manifestation and is associated with poor clinical outcomes. Chest imaging is often nonspecific, and symptoms can range from mild cough to acute respiratory distress syndrome (ARDS) . This is a case of a 49-year-old female with a history of recent clostridium difficile colitis status post treatment with oral vancomycin who presented with rash, acute liver and kidney failure, as well as diffuse nodular alveolar lung opacities concerning for DRESS syndrome with multi-organ involvement. Clinical Course: This patient initially presented to an outside hospital with clostridium difficile colitis, acute liver injury, and acute kidney injury. She developed a desquamating maculopapular rash in the setting of recent oral vancomycin, meloxicam, and furosemide initiation. She was hospitalized on two additional occasions with worsening altered mental status, liver injury, and acute kidney injury and was initiated on intermittent hemodialysis. Notably, she was found to have systemic eosinophilia (4100 cells/microliter) several weeks prior. She was transferred to this institution for further management where she was found to have encephalopathy, jaundice, lower extremity edema, and diffuse bilateral rhonchorous breath sounds on pulmonary examination. The patient was started on methylprednisolone for suspected DRESS syndrome. She underwent an evaluation for alternative causes of her organ failure. Her workup included a negative infectious, autoimmune, metabolic, toxic, and malignant work-up. Abdominal computed tomography (CT) and ultrasound were remarkable for evidence of hepatic steatosis and possible cirrhotic morphology. Additionally, a chest CT demonstrated diffuse and symmetric nodular alveolar lung opacities with peripheral sparing not consistent with acute respiratory distress syndrome or edema. Ultimately, her condition continued to decline, and she required intubation on several occasions. On hospital day 25 she succumbed to distributive shock in the setting of probable sepsis and multi-organ failure. Discussion: DRESS syndrome occurs in 1 in 1,000 to 10,000 patients with a mortality rate of around 10%. Anti-convulsant, anti-bacterial, anti-viral, and sulfonamide drugs are the most common drugs implicated in the development of DRESS syndrome; however, the list of offending agents is extensive . The diagnosis of DRESS syndrome is made after excluding other causes of disease such as infectious and autoimmune etiologies. The RegiSCAR scoring system is used to diagnose DRESS syndrome with 2-3 points indicating possible disease, 4-5 probable disease, and >5 definite disease. This patient scored a 7 on the RegiSCAR scale for eosinophilia, rash, organ involvement, and exclusion of other causes (infectious and autoimmune). While the pharmacologic trigger in this case is unknown, it is speculated to be caused by vancomycin, meloxicam, or furosemide due to the favorable timeline of initiation. Despite aggressive treatment, DRESS syndrome can often be fatal. Because of this, early diagnosis and treatment of patients with suspected DRESS syndrome is imperative.

Keywords: drug reaction with eosinophilia and systemic symptoms, multi-organ failure, pulmonary involvement, renal failure

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11 Evaluation of Coal Quality and Geomechanical Moduli Using Core and Geophysical Logs: Study from Middle Permian Barakar Formation of Gondwana Coalfield

Authors: Joyjit Dey, Souvik Sen

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Middle Permian Barakar formation is the major economic coal bearing unit of vast east-west trending Damodar Valley basin of Gondwana coalfield. Primary sedimentary structures were studied from the core holes, which represent majorly four facies groups: sandstone dominated facies, sandstone-shale heterolith facies, shale facies and coal facies. Total eight major coal seams have been identified with the bottom most seam being the thickest. Laterally, continuous coal seams were deposited in the calm and quiet environment of extensive floodplain swamps. Channel sinuosity and lateral channel migration/avulsion results in lateral facies heterogeneity and coal splitting. Geophysical well logs (Gamma-Resistivity-Density logs) have been used to establish the vertical and lateral correlation of various litho units field-wide, which reveals the predominance of repetitive fining upwards cycles. Well log data being a permanent record, offers a strong foundation for generating log based property evaluation and helps in characterization of depositional units in terms of lateral and vertical heterogeneity. Low gamma, high resistivity, low density is the typical coal seam signatures in geophysical logs. Here, we have used a density cutoff of 1.6 g/cc as a primary discriminator of coal and the same has been employed to compute various coal assay parameters, which are ash, fixed carbon, moisture, volatile content, cleat porosity, vitrinite reflectance (VRo%), which were calibrated with the laboratory based measurements. The study shows ash content and VRo% increase from west to east (towards basin margin), while fixed carbon, moisture and volatile content increase towards west, depicting increased coal quality westwards. Seam wise cleat porosity decreases from east to west, this would be an effect of overburden, as overburden pressure increases westward with the deepening of basin causing more sediment packet deposited on the western side of the study area. Coal is a porous, viscoelastic material in which velocity and strain both change nonlinearly with stress, especially for stress applied perpendicular to the bedding plane. Usually, the coal seam has a high velocity contrast relative to its neighboring layers. Despite extensive discussion of the maceral and chemical properties of coal, its elastic characteristics have received comparatively little attention. The measurement of the elastic constants of coal presents many difficulties: sample-to-sample inhomogeneity and fragility and velocity dependence on stress, orientation, humidity, and chemical content. In this study, a conclusive empirical equation VS= 0.80VP-0.86 has been used to model shear velocity from compression velocity. Also the same has been used to compute various geomechanical moduli. Geomech analyses yield a Poisson ratio of 0.348 against coals. Average bulk modulus value is 3.97 GPA, while average shear modulus and Young’s modulus values are coming out as 1.34 and 3.59 GPA respectively. These middle Permian Barakar coals show an average 23.84 MPA uniaxial compressive strength (UCS) with 4.97 MPA cohesive strength and 0.46 as friction coefficient. The output values of log based proximate parameters and geomechanical moduli suggest a medium volatile Bituminous grade for the studied coal seams, which is found in the laboratory based core study as well.

Keywords: core analysis, coal characterization, geophysical log, geo-mechanical moduli

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10 Settings of Conditions Leading to Reproducible and Robust Biofilm Formation in vitro in Evaluation of Drug Activity against Staphylococcal Biofilms

Authors: Adela Diepoltova, Klara Konecna, Ondrej Jandourek, Petr Nachtigal

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A loss of control over antibiotic-resistant pathogens has become a global issue due to severe and often untreatable infections. This state is reflected in complicated treatment, health costs, and higher mortality. All these factors emphasize the urgent need for the discovery and development of new anti-infectives. One of the most common pathogens mentioned in the phenomenon of antibiotic resistance are bacteria of the genus Staphylococcus. These bacterial agents have developed several mechanisms against the effect of antibiotics. One of them is biofilm formation. In staphylococci, biofilms are associated with infections such as endocarditis, osteomyelitis, catheter-related bloodstream infections, etc. To author's best knowledge, no validated and standardized methodology evaluating candidate compound activity against staphylococcal biofilms exists. However, a variety of protocols for in vitro drug activity testing has been suggested, yet there are often fundamental differences. Based on our experience, a key methodological step that leads to credible results is to form a robust biofilm with appropriate attributes such as firm adherence to the substrate, a complex arrangement in layers, and the presence of extracellular polysaccharide matrix. At first, for the purpose of drug antibiofilm activity evaluation, the focus was put on various conditions (supplementation of cultivation media by human plasma/fetal bovine serum, shaking mode, the density of initial inoculum) that should lead to reproducible and robust in vitro staphylococcal biofilm formation in microtiter plate model. Three model staphylococcal reference strains were included in the study: Staphylococcus aureus (ATCC 29213), methicillin-resistant Staphylococcus aureus (ATCC 43300), and Staphylococcus epidermidis (ATCC 35983). The total biofilm biomass was quantified using the Christensen method with crystal violet, and results obtained from at least three independent experiments were statistically processed. Attention was also paid to the viability of the biofilm-forming staphylococcal cells and the presence of extracellular polysaccharide matrix. The conditions that led to robust biofilm biomass formation with attributes for biofilms mentioned above were then applied by introducing an alternative method analogous to the commercially available test system, the Calgary Biofilm Device. In this test system, biofilms are formed on pegs that are incorporated into the lid of the microtiter plate. This system provides several advantages (in situ detection and quantification of biofilm microbial cells that have retained their viability after drug exposure). Based on our preliminary studies, it was found that the attention to the peg surface and substrate on which the bacterial biofilms are formed should also be paid to. Therefore, further steps leading to the optimization were introduced. The surface of pegs was coated by human plasma, fetal bovine serum, and L-polylysine. Subsequently, the willingness of bacteria to adhere and form biofilm was monitored. In conclusion, suitable conditions were revealed, leading to the formation of reproducible, robust staphylococcal biofilms in vitro for the microtiter model and the system analogous to the Calgary biofilm device, as well. The robustness and typical slime texture could be detected visually. Likewise, an analysis by confocal laser scanning microscopy revealed a complex three-dimensional arrangement of biofilm forming organisms surrounded by an extracellular polysaccharide matrix.

Keywords: anti-biofilm drug activity screening, in vitro biofilm formation, microtiter plate model, the Calgary biofilm device, staphylococcal infections, substrate modification, surface coating

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9 The Use of Rule-Based Cellular Automata to Track and Forecast the Dispersal of Classical Biocontrol Agents at Scale, with an Application to the Fopius arisanus Fruit Fly Parasitoid

Authors: Agboka Komi Mensah, John Odindi, Elfatih M. Abdel-Rahman, Onisimo Mutanga, Henri Ez Tonnang

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Ecosystems are networks of organisms and populations that form a community of various species interacting within their habitats. Such habitats are defined by abiotic and biotic conditions that establish the initial limits to a population's growth, development, and reproduction. The habitat’s conditions explain the context in which species interact to access resources such as food, water, space, shelter, and mates, allowing for feeding, dispersal, and reproduction. Dispersal is an essential life-history strategy that affects gene flow, resource competition, population dynamics, and species distributions. Despite the importance of dispersal in population dynamics and survival, understanding the mechanism underpinning the dispersal of organisms remains challenging. For instance, when an organism moves into an ecosystem for survival and resource competition, its progression is highly influenced by extrinsic factors such as its physiological state, climatic variables and ability to evade predation. Therefore, greater spatial detail is necessary to understand organism dispersal dynamics. Understanding organisms dispersal can be addressed using empirical and mechanistic modelling approaches, with the adopted approach depending on the study's purpose Cellular automata (CA) is an example of these approaches that have been successfully used in biological studies to analyze the dispersal of living organisms. Cellular automata can be briefly described as occupied cells by an individual that evolves based on proper decisions based on a set of neighbours' rules. However, in the ambit of modelling individual organisms dispersal at the landscape scale, we lack user friendly tools that do not require expertise in mathematical models and computing ability; such as a visual analytics framework for tracking and forecasting the dispersal behaviour of organisms. The term "visual analytics" (VA) describes a semiautomated approach to electronic data processing that is guided by users who can interact with data via an interface. Essentially, VA converts large amounts of quantitative or qualitative data into graphical formats that can be customized based on the operator's needs. Additionally, this approach can be used to enhance the ability of users from various backgrounds to understand data, communicate results, and disseminate information across a wide range of disciplines. To support effective analysis of the dispersal of organisms at the landscape scale, we therefore designed Pydisp which is a free visual data analytics tool for spatiotemporal dispersal modeling built in Python. Its user interface allows users to perform a quick and interactive spatiotemporal analysis of species dispersal using bioecological and climatic data. Pydisp enables reuse and upgrade through the use of simple principles such as Fuzzy cellular automata algorithms. The potential of dispersal modeling is demonstrated in a case study by predicting the dispersal of Fopius arisanus (Sonan), endoparasitoids to control Bactrocera dorsalis (Hendel) (Diptera: Tephritidae) in Kenya. The results obtained from our example clearly illustrate the parasitoid's dispersal process at the landscape level and confirm that dynamic processes in an agroecosystem are better understood when designed using mechanistic modelling approaches. Furthermore, as demonstrated in the example, the built software is highly effective in portraying the dispersal of organisms despite the unavailability of detailed data on the species dispersal mechanisms.

Keywords: cellular automata, fuzzy logic, landscape, spatiotemporal

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8 Bio-Electro Chemical Catalysis: Redox Interactions, Storm and Waste Water Treatment

Authors: Michael Radwan Omary

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Context: This scientific innovation demonstrate organic catalysis engineered media effective desalination of surface and groundwater. The author has developed a technology called “Storm-Water Ions Filtration Treatment” (SWIFTTM) cold reactor modules designed to retrofit typical urban street storm drains or catch basins. SWIFT triggers biochemical redox reactions with water stream-embedded toxic total dissolved solids (TDS) and electrical conductivity (EC). SWIFTTM Catalysts media unlock the sub-molecular bond energy, break down toxic chemical bonds, and neutralize toxic molecules, bacteria and pathogens. Research Aim: This research aims to develop and design lower O&M cost, zero-brine discharge, energy input-free, chemical-free water desalination and disinfection systems. The objective is to provide an effective resilient and sustainable solution to urban storm-water and groundwater decontamination and disinfection. Methodology: We focused on the development of organic, non-chemical, no-plugs, no pumping, non-polymer and non-allergenic approaches for water and waste water desalination and disinfection. SWIFT modules operate by directing the water stream to flow freely through the electrically charged media cold reactor, generating weak interactions with a water-dissolved electrically conductive molecule, resulting in the neutralization of toxic molecules. The system is powered by harvesting sub-molecular bonds embedded in energy. Findings: The SWIFTTM Technology case studies at CSU-CI and CSU-Fresno Water Institute, demonstrated consistently high reduction of all 40 detected waste-water pollutants including pathogens to levels below a state of California Department of Water Resources “Drinking Water Maximum Contaminants Levels”. The technology has proved effective in reducing pollutants such as arsenic, beryllium, mercury, selenium, glyphosate, benzene, and E. coli bacteria. The technology has also been successfully applied to the decontamination of dissolved chemicals, water pathogens, organic compounds and radiological agents. Theoretical Importance: SWIFT technology development, design, engineering, and manufacturing, offer cutting-edge advancement in achieving clean-energy source bio-catalysis media solution, an energy input free water and waste water desalination and disinfection. A significant contribution to institutions and municipalities achieving sustainable, lower cost, zero-brine and zero CO2 discharges clean energy water desalination. Data Collection and Analysis Procedures: The researchers collected data on the performance of the SWIFTTM technology in reducing the levels of various pollutants in water. The data was analyzed by comparing the reduction achieved by the SWIFTTM technology to the Drinking Water Maximum Contaminants Levels set by the state of California. The researchers also conducted live oral presentations to showcase the applications of SWIFTTM technology in storm water capture and decontamination as well as providing clean drinking water during emergencies. Conclusion: The SWIFTTM Technology has demonstrated its capability to effectively reduce pollutants in water and waste water to levels below regulatory standards. The Technology offers a sustainable solution to groundwater and storm-water treatments. Further development and implementation of the SWIFTTM Technology have the potential to treat storm water to be reused as a new source of drinking water and an ambient source of clean and healthy local water for recharge of ground water.

Keywords: catalysis, bio electro interactions, water desalination, weak-interactions

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7 Human Behaviour During an Earthquake: Descriptive Analysis on Indoor Video Recordings

Authors: Mazlum Çelik, Burcu Gürkan Ercan, Ahmet Ayaz, Hilal Yakut İpekoğlu, Furkan Baltacı, Mustafa Kurtoğlu, Bilge Kalkavan, Sinem Küçükyılmaz, Hikmet Çağrı Yardımcı, Şeyma Sevgican, Cemile Gökçe Elkovan, Bilal Çayır, Mehmet Emin Düzcan

Abstract:

The earthquake research literature generally examines emotional, cognitive, and behavioral responses after an earthquake. Studies concerning the behavioral responses to earthquakes reveal that after the earthquake, people either flee in a panic or do not act according to the stereotype that they act irrationally and anti-socially and sometimes give rational and adaptive reactions. However, the rareness of research dealing with human behavior experiencing the earthquake moment makes it necessary to pay particular attention to these behavior patterns. In this direction, this study aims to examine human behavior indoors in case of rising earthquake intensity. In Turkey, located on geography in the earthquake zone, devastating earthquakes took place, such as in "Istanbul" with a magnitude of 7.4 in 1999 and in "Elazığ" with a magnitude of 6.8 in 2020. Occurred recently, the "Kahramanmaraş" earthquake affected 11 provinces, with a magnitude of 7.7 and 7.6 in 2023. In addition, there is expected to be a devastating earthquake in Istanbul, experts warn. For this reason, it is essential to understand human behavior for disaster risk. Management and pre-disaster preparedness to be effective and efficient and to take realistic measures to protect human life. Mazlum Çelik, Burcu Gürkan Ercan, Ahmet Ayaz, Hilal Yakut İpekoğlu, Furkan Baltacı, Mustafa Kurtoğlu, Bilge Kalkavan, Sinem Küçükyılmaz, Hikmet Çağrı Yardımcı, Şeyma Sevgican, Cemile Gökçe Elkovan, Bilal Çayır, Mehmet Emin Düzcan. In this study, which is currently part of a project supported by The Scientific and Technological Council of Turkey (TUBITAK), the indoor recordings during the earthquakes in Elazig on January 24, 2020, and in İzmir on October 30, 2020, are examined, and the people's behavior during the earthquake is analyzed. In this direction, video recordings taken from the YouTube archives of İzmir and Elazığ Disaster and Emergency Management Presidency (AFAD) Directorates and metropolitan municipalities are examined. The researchers have created an observation form in line with the information in the relevant literature to classify people's behavior during an earthquake. It is intended to determine the behavioral patterns by classifying according to the form and video analysis of the people heading toward the door, remaining stable, taking protective measures, turning to people, and engaging in "other" behaviors outside of these behaviors during the earthquake. A total of 60 video analyzes are carried out from Elazığ and İzmir. The descriptive statistic has been used with the SPSS 23.0 package program in the data analysis. It is found that in the event of an increase in the severity of the earthquake, unlike Elazığ, in İzmir, protective action is preferred to the act of remaining stable. In addition, it is observed that with the increase in the earthquake's intensity, women attempt to take more protective action while men head toward the door. In contrast, a rise is observed in the behavior of young people heading toward the door and taking protective actions, while there is a decrease in their behavior directing to people. These findings, unlike the literature, reveal that human behavior during earthquakes cannot be reduced to a single behavior pattern, such as drop-cover-hold-on. The results show that it is necessary to understand the behaviors of individuals during the earthquake and to develop practical policy proposals for combating earthquakes by considering sociocultural, geographical, and demographic variables.

Keywords: descriptive analysis, earthquake, human behaviour, disaster policy.

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6 Exploratory Characterization of Antibacterial Efficacy of Synthesized Nanoparticles on Staphylococcus Isolates from Hospital Specimens in Saudi Arabia

Authors: Reham K. Sebaih, Afaf I. Shehata , Awatif A. Hindi, Tarek Gheith, Amal A. Hazzani Anas Al-Orjan

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Staphylococci spp are ubiquitous gram-positive bacteria is often associated with infections, especially nosocomial infections, and antibiotic resistanceStudy pathogenic bacteria and its use as a tool in the technology of Nano biology and molecular genetics research of the latest research trends of modern characterization and definition of different multiresistant of bacteria including Staphylococci. The Staphylococci are widespread all over the world and particularly in Saudi Arabia The present work study was conducted to evaluate the effect of five different types of nanoparticles (biosynthesized zinc oxide, Spherical and rod of each silver and gold nanoparticles) and their antibacterial impact on the Staphylococcus species. Ninety-six isolates of Staphylococcus species. Staphylococcus aureus, Staphylococcus epidermidis, MRSA were collected from different sources during the period between March 2011G to June 2011G. All isolates were isolated from inpatients and outpatients departments at Royal Commission Hospital in Yanbu Industrial, Saudi Arabia. High percentage isolation from males(55%) than females (45%). Staphylococcus epidermidis from males was (47%), (28%), and(25%). For Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus (MRSA. Isolates from females were Staphylococcus aureus with higher percent of (47%), (30%), and (23%) for MRSA, Staphylococcus epidermidis. Staphylococcus aureus from wound swab were the highest percent (51.42%) followed by vaginal swab (25.71%). Staphylococcus epidermidis were founded with higher percentage in blood (37.14%) and wound swab (34.21%) respectively related to other. The highest percentage of methicillin-resistant Staphylococcus aureus (MRSA)(80.77%) were isolated from wound swab, while those from nostrils were (19.23%). Staphylococcus species were isolates in highest percentage from hospital Emergency department with Staphylococcus aureus (59.37%), Methicillin-resistant Staphylococcus aureus (MRSA) (28.13%)and Staphylococcus epidermidis (12.5%) respectively. Evaluate the antibacterial property of Zinc oxide, Silver, and Gold nanoparticles as an alternative to conventional antibacterial agents Staphylococci isolates from hospital sources we screened them. Gold and Silver rods Nanoparticles to be sensitive to all isolates of Staphylococcus species. Zinc oxide Nanoparticles gave sensitivity impact range(52%) and (48%). The Gold and Silver spherical nanoparticles did not showed any effect on Staphylococci species. Zinc Oxide Nanoparticles gave bactericidal impact (25%) and bacteriostatic impact (75%) for of Staphylococci species. Detecting the association of nanoparticles with Staphylococci isolates imaging by scanning electron microscope (SEM) of some bacteriostatic isolates for Zinc Oxide nanoparticles on Staphylococcus aureus, Staphylococcus epidermidis and Methicillin resistant Staphylococcus aureus(MRSA), showed some Overlapping Bacterial cells with lower their number and appearing some appendages with deformities in external shape. Molecular analysis was applied by Multiplex polymerase chain reaction (PCR) used for the identification of genes within Staphylococcal pathogens. A multiplex polymerase chain reaction (PCR) method has been developed using six primer pairs to detect different genes using 50bp and 100bp DNA ladder marker. The range of Molecular gene typing ranging between 93 bp to 326 bp for Staphylococcus aureus and Methicillin resistant Staphylococcus aureus by TSST-1,mecA,femA and eta, while the bands border were from 546 bp to 682 bp for Staphylococcus epidermidis using icaAB and atlE. Sixteen isolation of Staphylococcus aureus and Methicillin resistant Staphylococcus aureus were positive for the femA gene at 132bp,this allowed the using of this gene as an internal positive control, fifteen isolates of Staphylococcus aureus and Methicillin resistant Staphylococcus aureus were positive for mecA gene at163bp.This gene was responsible for antibiotic resistant Methicillin, Two isolates of Staphylococcus aureus and Methicillin resistant Staphylococcus aureus were positive for the TSST-1 gene at326bp which is responsible for toxic shock syndrome in some Staphylococcus species, None were positive for eta gene at 102bpto that was responsible for Exfoliative toxins. Six isolates of Staphylococcus epidermidis were positive for atlE gene at 682 bp which is responsible for the initial adherence, three isolates of Staphylococcus epidermidis were positive for icaAB gene at 546bp that are responsible for mediates the formation of the biofilm. In conclusion, this study demonstrates the ability of the detection of the genes to discriminate between infecting Staphylococcus strains and considered biological tests, they may potentiate the clinical criteria used for the diagnosis of septicemia or catheter-related infections.

Keywords: multiplex polymerase chain reaction, toxic shock syndrome, Staphylococcus aureus, nosocomial infections

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5 White-Rot Fungi Phellinus as a Source of Antioxidant and Antitumor Agents

Authors: Yogesh Dalvi, Ruby Varghese, Nibu Varghese, C. K. Krishnan Nair

Abstract:

Introduction: The Genus Phellinus, locally known as Phansomba is a well-known traditional folk medicine. Especially, in Western Ghats of India, many tribes use several species of Phellinus for various ailments related to teeth, throat, tongue, stomach and even wound healing. It is one of the few mushrooms which play a pivotal role in Ayurvedic Dravyaguna. Aim: The present study focuses on to investigate phytochemical analysis, antioxidant, and antitumor (in vitro and in vivo) potential of Phellinus robinae from South India, Kerala Material and Methods: The present study explores the following: 1. Phellinus samples were collected from Ranni, Pathanamthitta district of Kerala state, India from Artocarpus heterophyllus Lam. and species were identified using rDNA region. 2. The fruiting body was shadow dried, powdered and extracted with 50% alcohol using water bath at 60°C which was further condensed by rotary evaporator and lyophilized at minus 40°C temperature. 3. Secondary metabolites were analyzed by using various phytochemical screening assay (Hager’s Test, Wagner’s Test, Sodium hydroxide Test, Lead acetate Test, Ferric chloride Test, Folin-ciocalteu Test, Foaming Test, Benedict’s test, Fehling’s Test and Lowry’s Test). 4. Antioxidant and free radical scavenging activity were analyzed by DPPH, FRAP and Iron chelating assay. 5. The antitumor potential of Water alcohol extract of Phellinus (PAWE) is evaluated through In vitro condition by Trypan blue dye exclusion method in DLA cell line and In vivo by murine model. Result and Discussion: Preliminary phytochemical screening by various biochemical tests revealed presence of a variety of active secondary molecules like alkaloids, flavanoids, saponins, carbohydrate, protein and phenol. In DPPH and FRAP assay PAWE showed significantly higher antioxidant activity as compared to standard Ascorbic acid. While, in Iron chelating assay, PAWE exhibits similar antioxidant activity that of Butylated Hydroxytoluene (BHT) as standard. Further, in the in vitro study, PAWE showed significant inhibition on DLA cell proliferation in dose dependent manner and showed no toxicity on mice splenocytes, when compared to standard chemotherapy drug doxorubicin. In vivo study, oral administration of PAWE showed dose dependent tumor regression in mice and also raised the immunogenicity by restoring levels of antioxidant enzymes in liver and kidney tissue. In both in vitro and in vivo gene expression studies PAWE up-regulates pro-apoptotic genes (Bax, Caspases 3, 8 and 9) and down- regulates anti-apoptotic genes (Bcl2). PAWE also down regulates inflammatory gene (Cox-2) and angiogenic gene (VEGF). Conclusion: Preliminary phytochemical screening revealed that PAWE contains various secondary metabolites which contribute to its antioxidant and free radical scavenging property as evaluated by DPPH, FRAP and Iron chelating assay. PAWE exhibits anti-proliferative activity by the induction of apoptosis through a signaling cascade of death receptor-mediated extrinsic (Caspase8 and Tnf-α), as well as mitochondria-mediated intrinsic (caspase9) and caspase pathways (Caspase3, 8 and 9) and also by regressing angiogenic factor (VEGF) without any inflammation or adverse side effects. Hence, PAWE serve as a potential antioxidant and antitumor agent.

Keywords: antioxidant, antitumor, Dalton lymphoma ascites (DLA), fungi, Phellinus robinae

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4 Temporal Profile of T2 MRI and 1H-MRS in the MDX Mouse Model of Duchenne Muscular Dystrophy

Authors: P. J. Sweeney, T. Ahtoniemi, J. Puoliväli, T. Laitinen, K.Lehtimäki, A. Nurmi, D. Wells

Abstract:

Duchenne muscular dystrophy (DMD) is an X-linked, lethal muscle wasting disease for which there are currently no treatment that effectively prevents the muscle necrosis and progressive muscle loss. DMD is among the most common of inherited diseases affecting around 1/3500 live male births. MDX (X-linked muscular dystrophy) mice only partially encapsulate the disease in humans and display weakness in muscles, muscle damage and edema during a period deemed the “critical period” when these mice go through cycles of muscular degeneration and regeneration. Although the MDX mutant mouse model has been extensively studied as a model for DMD, to-date an extensive temporal, non-invasive imaging profile that utilizes magnetic resonance imaging (MRI) and 1H-magnetic resonance spectroscopy (1H-MRS) has not been performed.. In addition, longitudinal imaging characterization has not coincided with attempts to exacerbate the progressive muscle damage by exercise. In this study we employed an 11.7 T small animal MRI in order to characterize the MRI and MRS profile of MDX mice longitudinally during a 12 month period during which MDX mice were subjected to exercise. Male mutant MDX mice (n=15) and male wild-type mice (n=15) were subjected to a chronic exercise regime of treadmill walking (30 min/ session) bi-weekly over the whole 12 month follow-up period. Mouse gastrocnemius and tibialis anterior muscles were profiled with baseline T2-MRI and 1H-MRS at 6 weeks of age. Imaging and spectroscopy was repeated again at 3 months, 6 months, 9 months and 12 months of age. Plasma creatine kinase (CK) level measurements were coincided with time-points for T2-MRI and 1H-MRS, but also after the “critical period” at 10 weeks of age. The results obtained from this study indicate that chronic exercise extends dystrophic phenotype of MDX mice as evidenced by T2-MRI and1H-MRS. T2-MRI revealed extent and location of the muscle damage in gastrocnemius and tibialis anterior muscles as hyperintensities (lesions and edema) in exercised MDX mice over follow-up period.. The magnitude of the muscle damage remained stable over time in exercised mice. No evident fat infiltration or cumulation to the muscle tissues was seen at any time-point in exercised MDX mice. Creatine, choline and taurine levels evaluated by 1H-MRS from the same muscles were found significantly decreased in each time-point, Extramyocellular (EMCL) and intramyocellular lipids (IMCL) did not change in exercised mice supporting the findings from anatomical T2-MRI scans for fat content. Creatine kinase levels were found to be significantly higher in exercised MDX mice during the follow-up period and importantly CK levels remained stable over the whole follow-up period. Taken together, we have described here longitudinal prophile for muscle damage and muscle metabolic changes in MDX mice subjected to chronic exercised. The extent of the muscle damage by T2-MRI was found to be stable through the follow-up period in muscles examined. In addition, metabolic profile, especially creatine, choline and taurine levels in muscles, was found to be sustained between time-points. The anatomical muscle damage evaluated by T2-MRI was supported by plasma CK levels which remained stable over the follow-up period. These findings show that non-invasive imaging and spectroscopy can be used effectively to evaluate chronic muscle pathology. These techniques can be also used to evaluate the effect of various manipulations, like here exercise, on the phenotype of the mice. Many of the findings we present here are translatable to clinical disease, such as decreased creatine, choline and taurine levels in muscles. Imaging by T2-MRI and 1H-MRS also revealed that fat content or extramyocellar and intramyocellular lipids, respectively, are not changed in MDX mice, which is in contrast to clinical manifestation of the Duchenne’s muscle dystrophy. Findings show that non-invasive imaging can be used to characterize the phenotype of a MDX model and its translatability to clinical disease, and to study events that have traditionally been not examined, like here rigorous exercise related sustained muscle damage after the “critical period”. The ability for this model to display sustained damage beyond the spontaneous “critical period“ and in turn to study drug effects on this extended phenotype will increase the value of the MDX mouse model as a tool to study therapies and treatments aimed at DMD and associated diseases.

Keywords: 1H-MRS, MRI, muscular dystrophy, mouse model

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3 Amifostine Analogue, Drde-30, Attenuates Radiation-Induced Lung Injury in Mice

Authors: Aastha Arora, Vikas Bhuria, Saurabh Singh, Uma Pathak, Shweta Mathur, Puja P. Hazari, Rajat Sandhir, Ravi Soni, Anant N. Bhatt, Bilikere S. Dwarakanath

Abstract:

Radiotherapy is an effective curative and palliative option for patients with thoracic malignancies. However, lung injury, comprising of pneumonitis and fibrosis, remains a significant clin¬ical complication of thoracic radiation, thus making it a dose-limiting factor. Also, injury to the lung is often reported as part of multi-organ failure in victims of accidental radiation exposures. Radiation induced inflammatory response in the lung, characterized by leukocyte infiltration and vascular changes, is an important contributing factor for the injury. Therefore, countermeasure agents to attenuate radiation induced inflammatory response are considered as an important approach to prevent chronic lung damage. Although Amifostine, the widely used, FDA approved radio-protector, has been found to reduce the radiation induced pneumonitis during radiation therapy of non-small cell lung carcinoma, its application during mass and field exposure is limited due to associated toxicity and ineffectiveness with the oral administration. The amifostine analogue (DRDE-30) overcomes this limitation as it is orally effective in reducing the mortality of whole body irradiated mice. The current study was undertaken to investigate the potential of DRDE-30 to ameliorate radiation induced lung damage. DRDE-30 was administered intra-peritoneally, 30 minutes prior to 13.5 Gy thoracic (60Co-gamma) radiation in C57BL/6 mice. Broncheo- alveolar lavage fluid (BALF) and lung tissues were harvested at 12 and 24 weeks post irradiation for studying inflammatory and fibrotic markers. Lactate dehydrogenase (LDH) leakage, leukocyte count and protein content in BALF were used as parameters to evaluate lung vascular permeability. Inflammatory cell signaling (p38 phosphorylation) and anti-oxidant status (MnSOD and Catalase level) was assessed by Western blot, while X-ray CT scan, H & E staining and trichrome staining were done to study the lung architecture and collagen deposition. Irradiation of the lung increased the total protein content, LDH leakage and total leukocyte count in the BALF, reflecting endothelial barrier dysfunction. These disruptive effects were significantly abolished by DRDE-30, which appear to be linked to the DRDE-30 mediated abrogation of activation of the redox-sensitive pro- inflammatory signaling cascade, the MAPK pathway. Concurrent administration of DRDE-30 with radiation inhibited radiation-induced oxidative stress by strengthening the anti-oxidant defense system and abrogated p38 mitogen-activated protein kinase activation, which was associated with reduced vascular leak and macrophage recruitment to the lungs. Histopathological examination (by H & E staining) of the lung showed radiation-induced inflammation of the lungs, characterized by cellular infiltration, interstitial oedema, alveolar wall thickening, perivascular fibrosis and obstruction of alveolar spaces, which were all reduced by pre-administration of DRDE-30. Structural analysis with X-ray CT indicated lung architecture (linked to the degree of opacity) comparable to un-irradiated mice that correlated well with the lung morphology and reduced collagen deposition. Reduction in the radiation-induced inflammation and fibrosis brought about by DRDE-30 resulted in a profound increase in animal survival (72 % in the combination vs 24% with radiation) observed at the end of 24 weeks following irradiation. These findings establish the potential of the Amifostine analogue, DRDE-30, in reducing radiation induced pulmonary injury by attenuating the inflammatory and fibrotic responses.

Keywords: amifostine, fibrosis, inflammation, lung injury radiation

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2 Research on a Digital Basketball Sports Game (DBSG) Framework Based on the Female Perspective

Authors: Ran Yue, Zhejing Li

Abstract:

Context: The context of this study is the field of Digital Basketball Sports Games (DBSG). The existing DBSGs often prioritize competitiveness and confrontation, neglecting the narrative and progressive expression, especially from a female standpoint. This study aims to address this gap by analyzing existing DBSGs and proposing a comprehensive framework tailored to meet the needs and desires of women in basketball. Research Aim: The aim of this research is to examine the narrative perspectives of women in basketball and understand their desires and expectations within the sport. It also seeks to investigate methods to seamlessly integrate women's basketball stories into gameplay, addressing their specific needs and expectations. Additionally, the study aims to develop a digital basketball sports game framework that combines narrative richness and entertainment, with a focus on the female audience. Methodology: The study utilizes affective-arousal theories as a psychological framework to explore how emotional arousal influences player engagement and responses in the digital basketball sports game. It employs in-depth case studies to examine specific instances and gain insights into the implementation and impact of narrative elements and educational features in existing DBSGs. Comparative studies are conducted to analyze different DBSGs, identifying effective strategies and shortcomings. Findings: The research findings contribute to the development of a digital basketball game framework from a female perspective. This framework enhances the completeness, diversity, and inclusivity of digital basketball sports games. By addressing the specific needs of women in basketball, including fundamental knowledge, sports skills, safety awareness, and rehabilitation training methods, the framework provides a foundational reservoir for a broader range of basketball participation. It enriches the gaming experience by enhancing enjoyment, narrative, and diversity. It also acts as a catalyst to encourage more women to engage with basketball stories, participate in the sport, persevere, and derive greater enjoyment while benefiting their physical fitness and health. Theoretical Importance: The study contributes to the existing literature by incorporating game motivation psychology theories and proposing a comprehensive framework that caters to the specific needs of women in basketball. It emphasizes the importance of considering the narrative and progressive expression in DBSGs, especially from a female perspective. The research explores affective-arousal theories and provides insights into how emotional arousal can influence player engagement and responses in digital basketball sports games. Data Collection and Analysis Procedures: The study collects data through in-depth case studies of existing DBSGs, examining specific instances to uncover insights into the implementation and impact of narrative elements and educational features. Comparative studies are conducted to contrast and analyze various DBSGs, identifying effective strategies and shortcomings. The analysis procedures involve identifying commonalities, differences, strengths, and weaknesses among the DBSGs, guiding the development of a female-centric perspective in the proposed framework. Questions Addressed: The study addresses the following questions: What are the narrative perspectives of women in basketball? How can women's basketball stories be seamlessly integrated into gameplay? What are the specific needs and expectations of women in basketball? What effective strategies and shortcomings exist in current DBSGs? How can a digital basketball game framework be developed to cater to the female audience? Conclusion: In conclusion, this study contributes to the field of DBSGs by proposing a comprehensive digital basketball game framework from a female perspective. The framework enhances the inclusivity, diversity, and enjoyment of DBSGs by addressing the specific needs and desires of women in basketball. It provides a foundation for a broader range of basketball participation, enriching the gaming experience and benefiting women's physical fitness and health. The research, using affective-arousal theories and in-depth case studies, provides valuable insights into the implementation and impact of narrative elements and educational features in existing DBSGs, guiding the development of the proposed female-centric framework.

Keywords: digital basketball game, game framework, female perspective, game narratives

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1 Glycyrrhizic Acid Inhibits Lipopolysaccharide-Stimulated Bovine Fibroblast-Like Synoviocyte, Invasion through Suppression of TLR4/NF-κB-Mediated Matrix Metalloproteinase-9 Expression

Authors: Hosein Maghsoudi

Abstract:

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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