Search results for: neutron activation
Commenced in January 2007
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Paper Count: 1117

Search results for: neutron activation

7 Radioprotective Effects of Super-Paramagnetic Iron Oxide Nanoparticles Used as Magnetic Resonance Imaging Contrast Agent for Magnetic Resonance Imaging-Guided Radiotherapy

Authors: Michael R. Shurin, Galina Shurin, Vladimir A. Kirichenko

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Background. Visibility of hepatic malignancies is poor on non-contrast imaging for daily verification of liver malignancies prior to radiation therapy on MRI-guided Linear Accelerators (MR-Linac). Ferumoxytol® (Feraheme, AMAG Pharmaceuticals, Waltham, MA) is a SPION agent that is increasingly utilized off-label as hepatic MRI contrast. This agent has the advantage of providing a functional assessment of the liver based upon its uptake by hepatic Kupffer cells proportionate to vascular perfusion, resulting in strong T1, T2 and T2* relaxation effects and enhanced contrast of malignant tumors, which lack Kupffer cells. The latter characteristic has been recently utilized for MRI-guided radiotherapy planning with precision targeting of liver malignancies. However potential radiotoxicity of SPION has never been addressed for its safe use as an MRI-contrast agent during liver radiotherapy on MRI-Linac. This study defines the radiomodulating properties of SPIONs in vitro on human monocyte and macrophage cell lines exposed to 60Go gamma-rays within clinical radiotherapy dose range. Methods. Human monocyte and macrophages cell line in cultures were loaded with a clinically relevant concentration of Ferumoxytol (30µg/ml) for 2 and 24 h and irradiated to 3Gy, 5Gy and 10Gy. Cells were washed and cultured for additional 24 and 48 h prior to assessing their phenotypic activation by flow cytometry and function, including viability (Annexin V/PI assay), proliferation (MTT assay) and cytokine expression (Luminex assay). Results. Our results reveled that SPION affected both human monocytes and macrophages in vitro. Specifically, iron oxide nanoparticles decreased radiation-induced apoptosis and prevented radiation-induced inhibition of human monocyte proliferative activity. Furthermore, Ferumoxytol protected monocytes from radiation-induced modulation of phenotype. For instance, while irradiation decreased polarization of monocytes to CD11b+CD14+ and CD11bnegCD14neg phenotype, Ferumoxytol prevented these effects. In macrophages, Ferumoxytol counteracted the ability of radiation to up-regulate cell polarization to CD11b+CD14+ phenotype and prevented radiation-induced down-regulation of expression of HLA-DR and CD86 molecules. Finally, Ferumoxytol uptake by human monocytes down-regulated expression of pro-inflammatory chemokines MIP-1α (Macrophage inflammatory protein 1α), MIP-1β (CCL4) and RANTES (CCL5). In macrophages, Ferumoxytol reversed the expression of IL-1RA, IL-8, IP-10 (CXCL10) and TNF-α, and up-regulates expression of MCP-1 (CCL2) and MIP-1α in irradiated macrophages. Conclusion. SPION agent Ferumoxytol increases resistance of human monocytes to radiation-induced cell death in vitro and supports anti-inflammatory phenotype of human macrophages under radiation. The effect is radiation dose-dependent and depends on the duration of Feraheme uptake. This study also finds strong evidence that SPIONs reversed the effect of radiation on the expression of pro-inflammatory cytokines involved in initiation and development of radiation-induced liver damage. Correlative translational work at our institution will directly assess the cyto-protective effects of Ferumoxytol on human Kupfer cells in vitro and ex vivo analysis of explanted liver specimens in a subset of patients receiving Feraheme-enhanced MRI-guided radiotherapy to the primary liver tumors as a bridge to liver transplant.

Keywords: superparamagnetic iron oxide nanoparticles, radioprotection, magnetic resonance imaging, liver

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6 Musictherapy and Gardentherapy: A Systemic Approach for the Life Quality of the PsychoPhysical Disability

Authors: Adriana De Serio, Donato Forenza

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Aims. In this experimental research the Authors present the methodological plan “Musictherapy and Gardentherapy” that they created interconnected with the garden landscape ecosystems and aimed at PsychoPhysical Disability (MusGarPPhyD). In the context of the environmental education aimed at spreading the landscape culture and its values, it’s necessary to develop a solid perception of the environment sustainability to implement a multidimensional approach that pays attention to the conservation and enhancement of gardens and natural environments. The result is an improvement in the life quality also in compliance with the objectives of the European Agenda 2030. The MusGarPPhyD can help professionals such as musictherapists and environmental and landscape researchers strengthen subjects' motivation to learn to deal with the psychophysical discomfort associated with disability and to cope with the distress and the psychological fragility and the loneliness and the social seclusion and to promote productive social relationships. Materials and Methods. The MusGarPPhyD was implemented in multiple spaces. The musictherapy treatments took place first inside residential therapeutic centres and then in the garden landscape ecosystem. Patients: twenty, set in two groups. Weekly-sessions (50’) for three months. Methodological phases: - Phase P1. MusicTherapy treatments for each group in the indoor spaces. - Phase P2. MusicTherapy sessions inside the gardens. After each Phase, P1 and P2: - a Questionnaire for each patient (ten items / liking-indices) was administrated at t0 time, during the treatment and at tn time at the end of the treatment. - Monitoring of patients' behavioral responses through assessment scales, matrix, table and graph system. MusicTherapy methodology: pazient Sonorous-Musical Anamnesis, Musictherapy Assessment Document, Observation Protocols, Bodily-Environmental-Rhythmical-Sonorous-Vocal-Energy production first indoors and then outside, sonorous-musical instruments and edible instruments made by the Author/musictherapist with some foods; Administration of Patient-Environment-Music Index at time to and tn, to estimate the patient’s behavior evolution, Musictherapeutic Advancement Index. Results. The MusGarPPhyD can strengthen the individual sense of identity and improve the psychophysical skills and the resilience to face and to overcome the difficulties caused by the congenital /acquired disability. The multi-sensory perceptions deriving from contact with the plants in the gardens improve the psychological well-being and regulate the physiological parameters such as blood pressure, cardiac and respiratory rhythm, reducing the cholesterol levels. The secretions of the peptide hormones endorphins and the endogenous opioids enkephalins increase and bring a state of patient’s tranquillity and a better mood. The subjects showed a preference for musictherapy treatments within a setting made up of gardens and peculiar landscape systems. This resulted in greater health benefits. Conclusions. The MusGarPPhyD contributes to reduce psychophysical tensions, anxiety, depression and stress, facilitating the connections between the cerebral hemispheres, thus also improving intellectual performances, self-confidence, motor skills and social interactions. Therefore it is necessary to design hospitals, rehabilitation centers, nursing homes, surrounded by gardens. Ecosystems of natural and urban parks and gardens create fascinating skyline and mosaics of landscapes rich in beauty and biodiversity. The MusGarPPhyD is useful for the health management promoting patient’s psychophysical activation, better mood/affective-tone and relastionships and contributing significantly to improving the life quality.

Keywords: musictherapy, gardentherapy, disability, life quality

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5 Feasibility and Acceptability of an Emergency Department Digital Pain Self-Management Intervention: An Randomized Controlled Trial Pilot Study

Authors: Alexandria Carey, Angela Starkweather, Ann Horgas, Hwayoung Cho, Jason Beneciuk

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Background/Significance: Over 3.4 million acute axial low back pain (aLBP) cases are treated annually in the United States (US) emergency departments (ED). ED patients with aLBP receive varying verbal and written discharge routine care (RC), leading to ineffective patient self-management. Ineffective self-management increase chronic low back pain (cLPB) transition risks, a chief cause of worldwide disability, with associated costs >$60 million annually. This research addresses this significant problem by evaluating an ED digital pain self-management intervention (EDPSI) focused on improving self-management through improved knowledge retainment, skills, and self-efficacy (confidence) (KSC) thus reducing aLBP to cLBP transition in ED patients discharged with aLBP. The research has significant potential to increase self-efficacy, one of the most potent mechanisms of behavior change and improve health outcomes. Focusing on accessibility and usability, the intervention may reduce discharge disparities in aLBP self-management, especially with low health literacy. Study Questions: This research will answer the following questions: 1) Will an EDPSI focused on improving KSC progress patient self-management behaviors and health status?; 2) Is the EDPSI sustainable to improve pain severity, interference, and pain recurrence?; 3) Will an EDPSI reduce aLBP to cLBP transition in patients discharged with aLBP? Aims: The pilot randomized-controlled trial (RCT) study’s objectives assess the effects of a 12-week digital self-management discharge tool in patients with aLBP. We aim to 1) Primarily assess the feasibility [recruitment, enrollment, and retention], and [intervention] acceptability, and sustainability of EDPSI on participant’s pain self-management; 2) Determine the effectiveness and sustainability of EDPSI on pain severity/interference among participants. 3) Explore patient preferences, health literacy, and changes among participants experiencing the transition to cLBP. We anticipate that EDPSI intervention will increase likelihood of achieving self-management milestones and significantly improve pain-related symptoms in aLBP. Methods: The study uses a two-group pilot RCT to enroll 30 individuals who have been seen in the ED with aLBP. Participants are randomized into RC (n=15) or RC + EDPSI (n=15) and receive follow-up surveys for 12-weeks post-intervention. EDPSI innovative content focuses on 1) highlighting discharge education; 2) provides self-management treatment options; 3) actor demonstration of ergonomics, range of motion movements, safety, and sleep; 4) complementary alternative medicine (CAM) options including acupuncture, yoga, and Pilates; 5) combination therapies including thermal application, spinal manipulation, and PT treatments. The intervention group receives Booster sessions via Zoom to assess and reinforce their knowledge retention of techniques and provide return demonstration reinforcing ergonomics, in weeks two and eight. Outcome Measures: All participants are followed for 12-weeks, assessing pain severity/ interference using the Brief Pain Inventory short-form (BPI-sf) survey, self-management (measuring KSC) using the short 13-item Patient Activation Measure (PAM), and self-efficacy using the Pain Self-Efficacy Questionnaire (PSEQ) weeks 1, 6, and 12. Feasibility is measured by recruitment, enrollment, and retention percentages. Acceptability and education satisfaction are measured using the Education-Preference and Satisfaction Questionnaire (EPSQ) post-intervention. Self-management sustainment is measured including PSEQ, PAM, and patient satisfaction and healthcare utilization (PSHU) requesting patient overall satisfaction, additional healthcare utilization, and pain management related to continued back pain or complications post-injury.

Keywords: digital, pain self-management, education, tool

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4 Industrial Waste to Energy Technology: Engineering Biowaste as High Potential Anode Electrode for Application in Lithium-Ion Batteries

Authors: Pejman Salimi, Sebastiano Tieuli, Somayeh Taghavi, Michela Signoretto, Remo Proietti Zaccaria

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Increasing the growth of industrial waste due to the large quantities of production leads to numerous environmental and economic challenges, such as climate change, soil and water contamination, human disease, etc. Energy recovery of waste can be applied to produce heat or electricity. This strategy allows for the reduction of energy produced using coal or other fuels and directly reduces greenhouse gas emissions. Among different factories, leather manufacturing plays a very important role in the whole world from the socio-economic point of view. The leather industry plays a very important role in our society from a socio-economic point of view. Even though the leather industry uses a by-product from the meat industry as raw material, it is considered as an activity demanding integrated prevention and control of pollution. Along the entire process from raw skins/hides to finished leather, a huge amount of solid and water waste is generated. Solid wastes include fleshings, raw trimmings, shavings, buffing dust, etc. One of the most abundant solid wastes generated throughout leather tanning is shaving waste. Leather shaving is a mechanical process that aims at reducing the tanned skin to a specific thickness before tanning and finishing. This product consists mainly of collagen and tanning agent. At present, most of the world's leather processing is chrome-tanned based. Consequently, large amounts of chromium-containing shaving wastes need to be treated. The major concern about the management of this kind of solid waste is ascribed to chrome content, which makes the conventional disposal methods, such as landfilling and incineration, not practicable. Therefore, many efforts have been developed in recent decades to promote eco-friendly/alternative leather production and more effective waste management. Herein, shaving waste resulting from metal-free tanning technology is proposed as low-cost precursors for the preparation of carbon material as anodes for lithium-ion batteries (LIBs). In line with the philosophy of a reduced environmental impact, for preparing fully sustainable and environmentally friendly LIBs anodes, deionized water and carboxymethyl cellulose (CMC) have been used as alternatives to toxic/teratogen N-methyl-2- pyrrolidone (NMP) and to biologically hazardous Polyvinylidene fluoride (PVdF), respectively. Furthermore, going towards the reduced cost, we employed water solvent and fluoride-free bio-derived CMC binder (as an alternative to NMP and PVdF, respectively) together with LiFePO₄ (LFP) when a full cell was considered. These actions make closer to the 2030 goal of having green LIBs at 100 $ kW h⁻¹. Besides, the preparation of the water-based electrodes does not need a controlled environment and due to the higher vapour pressure of water in comparison with NMP, the water-based electrode drying is much faster. This aspect determines an important consequence, namely a reduced energy consumption for the electrode preparation. The electrode derived from leather waste demonstrated a discharge capacity of 735 mAh g⁻¹ after 1000 charge and discharge cycles at 0.5 A g⁻¹. This promising performance is ascribed to the synergistic effect of defects, interlayer spacing, heteroatoms-doped (N, O, and S), high specific surface area, and hierarchical micro/mesopore structure of the biochar. Interestingly, these features of activated biochars derived from the leather industry open the way for possible applications in other EESDs as well.

Keywords: biowaste, lithium-ion batteries, physical activation, waste management, leather industry

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3 The Impact of Neighborhood Effects on the Economic Mobility of the Inhabitants of Three Segregated Communities in Salvador (Brazil)

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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2 Mapping the Neurotoxic Effects of Sub-Toxic Manganese Exposure: Behavioral Outcomes, Imaging Biomarkers, and Dopaminergic System Alterations

Authors: Katie M. Clark, Adriana A. Tienda, Krista C. Paffenroth, Lindsey N. Brigante, Daniel C. Colvin, Jose Maldonado, Erin S. Calipari, Fiona E. Harrison

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Manganese (Mn) is an essential trace element required for human health and is important in antioxidant defenses, as well as in the development and function of dopaminergic neurons. However, chronic low-level Mn exposure, such as through contaminated drinking water, poses risks that may contribute to neurodevelopmental and neurodegenerative conditions, including attention deficit hyperactivity disorder (ADHD). Pharmacological inhibition of the dopamine transporter (DAT) blocks reuptake, elevates synaptic dopamine, and alleviates ADHD symptoms. This study aimed to determine whether Mn exposure in juvenile mice modifies their response to DAT blockers, amphetamine, and methylphenidate and utilize neuroimaging methods to visualize and quantify Mn distribution across dopaminergic brain regions. Male and female heterozygous DATᵀ³⁵⁶ᴹ and wild-type littermates were randomly assigned to receive control (2.5% Stevia) or high Manganese (2.5 mg/ml Mn + 2.5% Stevia) via water ad libitum from weaning (21-28 days) for 4-5 weeks. Mice underwent repeated testing in locomotor activity chambers for three consecutive days (60 mins.) to ensure that they were fully habituated to the environments. On the fourth day, a 3-hour activity session was conducted following treatment with amphetamine (3 mg/kg) or methylphenidate (5 mg/kg). The second drug was administered in a second 3-hour activity session following a 1-week washout period. Following the washout, the mice were given one last injection of amphetamine and euthanized one hour later. Using the ex-vivo brains, magnetic resonance relaxometry (MRR) was performed on a 7Telsa imaging system to map T1- and T2-weighted (T1W, T2W) relaxation times. Mn inherent paramagnetic properties shorten both T1W and T2W times, which enhances the signal intensity and contrast, enabling effective visualization of Mn accumulation in the entire brain. A subset of mice was treated with amphetamine 1 hour before euthanasia. SmartSPIM light sheet microscopy with cleared whole brains and cFos and tyrosine hydroxylase (TH) labeling enabled an unbiased automated counting and densitometric analysis of TH and cFos positive cells. Immunohistochemistry was conducted to measure synaptic protein markers and quantify changes in neurotransmitter regulation. Mn exposure elevated Mn brain levels and potentiated stimulant effects in males. The globus pallidus, substantia nigra, thalamus, and striatum exhibited more pronounced T1W shortening, indicating regional susceptibility to Mn accumulation (p<0.0001, 2-Way ANOVA). In the cleared whole brains, initial analyses suggest that TH and c-Fos co-staining mirrors behavioral data with decreased co-staining in DATT356M+/- mice. Ongoing studies will identify the molecular basis of the effect of Mn, including changes to DAergic metabolism and transport and post-translational modification to the DAT. These findings demonstrate that alterations in T1W relaxation times, as measured by MRR, may serve as an early biomarker for Mn neurotoxicity. This neuroimaging approach exhibits remarkable accuracy in identifying Mn-susceptible brain regions, with a spatial resolution and sensitivity that surpasses current conventional dissection and mass spectrometry approaches. The capability to label and map TH and cFos expression across the entire brain provides insights into whole-brain neuronal activation and its connections to functional neural circuits and behavior following amphetamine and methylphenidate administration.

Keywords: manganese, environmental toxicology, dopamine dysfunction, biomarkers, drinking water, light sheet microscopy, magnetic resonance relaxometry (MRR)

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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

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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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