Search results for: idiopathic inflammatory myopathies

Authors: Chengcao Sun, Cuili Yang, Shujun Li, Ruilin Xue, Yongyong Xi, Liang Wang, Dejia Li

Abstract:

Backgrounds: Inflammation is widely distributed in patients with Duchenne muscular dystrophy (DMD), and ultimately leads to progressive deterioration of muscle function with the co-effects of chronic muscle damage, oxidative stress, and reduced oxidative capacity. NF-E2-related factor 2 (Nrf2) plays a critical role in defending against inflammation in different tissues via activation of phase II enzymes, heme oxygenase-1 (HO-1). However, whether Nrf2/HO-1 pathway can attenuate muscle inflammation on DMD remains unknown. The purpose of this study was to determine the anti-inflammatory effects of Sulforaphane (SFN) on DMD. Methods: 4-week-old male mdx mice were treated with SFN by gavage (2 mg/kg body weight per day) for 4 weeks. Gastrocnemius, tibial anterior and triceps brachii muscles were collected for related analysis. Immune cell infiltration in skeletal muscles was analyzed by H&E staining and immuno-histochemistry. Moreover, the expressions of inflammatory cytokines,pro-inflammatory cytokines and Nrf2/HO-1 pathway were detected by western blot, qRT-PCR, immunohistochemistry and immunofluorescence assays. Results: Our results demonstrated that SFN treatment increased the expression of muscle phase II enzymes HO-1 in Nrf2 dependent manner. Inflammation in mdx skeletal muscles was reduced by SFN treatment as indicated by decreased immune cell infiltration and lower expressions of the inflammatory cytokines CD45, pro-inflammatory cytokines tumour necrosis factor-α and interleukin-6 in the skeletal muscles of mdx mice. Conclusions: Collectively, these results show that SFN can ameliorate muscle inflammation in mdx mice by Nrf2/HO-1 pathway, which indicates Nrf2/HO-1 pathway may represent a new therapeutic target for DMD.

Keywords: sulforaphane, Nrf2, HO-1, inflammation

Procedia PDF Downloads 334

Authors: Rania Melad Kamel Hakim

Abstract:

A descriptive statistical analysis of the data showed that the most important factor evoking negative attitudes among teachers is student behavior. These have been presented as useful models for understanding the risk factors and protective factors associated with the emergence of autistic traits. Although these ‘syndrome’ forms of autism reach clinical thresholds, they appear to be distinctly different from the idiopathic or ‘non-syndrome’ autism phenotype. Most teachers reported that kindergartens did not prepare them for the educational needs of children with autism, particularly in relation to non-verbal skills. The study is important and points the way to improving teacher inclusion education in Thailand. Inclusive education for students with autism is still in its infancy in Thailand. Although the number of autistic children in schools has increased significantly since the Thai government introduced the Education Regulations for Persons with Disabilities Act in 2008, there is a general lack of services for autistic students and their families. This quantitative study used the Teaching Skills and Readiness Scale for Students with Autism (APTSAS) to test the attitudes and readiness of 110 elementary school teachers when teaching students with autism in general education classrooms. To uncover the true nature of these co-morbidities, it is necessary to expand the definition of autism to include the cognitive features of the disorder and then apply this expanded conceptualization to examine patterns of autistic syndromes. This study used various established eye-tracking paradigms to assess the visual and attention performance of children with DS and FXS who meet the autism thresholds defined in the Social Communication Questionnaire. To study whether the autistic profiles of these children are associated with visual orientation difficulties (‘sticky attention’), decreased social attention, and increased visual search performance, all of which are hallmarks of the idiopathic autistic child phenotype. Data will be collected from children with DS and FXS, aged 6 to 10 years, and two control groups matched for age and intellectual ability (i.e., children with idiopathic autism).In order to enable a comparison of visual attention profiles, cross-sectional analyzes of developmental trajectories are carried out. Significant differences in the visual-attentive processes underlying the presentation of autism in children with FXS and DS have been suggested, supporting the concept of syndrome specificity. The study provides insights into the complex heterogeneity associated with autism syndrome symptoms and autism itself, with clinical implications for the utility of autism intervention programs in DS and FXS populations.

Keywords: attitude, autism, teachers, sports activities, movement skills, motor skills

Procedia PDF Downloads 54

Authors: Sara Asham Mahrous Kamel

Abstract:

A descriptive statistical analysis of the data showed that the most important factor evoking negative attitudes among teachers is student behavior. have been presented as useful models for understanding the risk factors and protective factors associated with the emergence of autistic traits. Although these "syndrome" forms of autism reach clinical thresholds, they appear to be distinctly different from the idiopathic or "non-syndrome" autism phenotype. Most teachers reported that kindergartens did not prepare them for the educational needs of children with autism, particularly in relation to non-verbal skills. The study is important and points the way for improving teacher inclusion education in Thailand. Inclusive education for students with autism is still in its infancy in Thailand. Although the number of autistic children in schools has increased significantly since the Thai government introduced the Education Regulations for Persons with Disabilities Act in 2008, there is a general lack of services for autistic students and their families. This quantitative study used the Teaching Skills and Readiness Scale for Students with Autism (APTSAS) to test the attitudes and readiness of 110 elementary school teachers when teaching students with autism in general education classrooms. To uncover the true nature of these co morbidities, it is necessary to expand the definition of autism to include the cognitive features of the disorder, and then apply this expanded conceptualization to examine patterns of autistic syndromes. This study used various established eye-tracking paradigms to assess the visual and attention performance of children with DS and FXS who meet the autism thresholds defined in the Social Communication Questionnaire. To study whether the autistic profiles of these children are associated with visual orientation difficulties ("sticky attention"), decreased social attention, and increased visual search performance, all of which are hallmarks of the idiopathic autistic child phenotype. Data will be collected from children with DS and FXS, aged 6 to 10 years, and two control groups matched for age and intellectual ability (i.e., children with idiopathic autism).In order to enable a comparison of visual attention profiles, cross-sectional analyzes of developmental trajectories are carried out. Significant differences in the visual-attentive processes underlying the presentation of autism in children with FXS and DS have been suggested, supporting the concept of syndrome specificity. The study provides insights into the complex heterogeneity associated with autism syndrome symptoms and autism itself, with clinical implications for the utility of autism intervention programs in DS and FXS populations.

Keywords: attitude, autism, teachers, sports activities, movement skills, motor skills

Procedia PDF Downloads 55

Authors: Tong-Chien Wu, Ching-Liang Hsieh, Yi-Wen Lin

Abstract:

There are accumulating evidences surrounding the therapeutic effect of electroacupuncture (EA). Local EA can reliably attenuate inflammatory pain in mouse with unclear mechanisms. However, the effect of EA on distal and contralateral acupoint for pain control has been rarely studied and the result was controversial. Here in our study, we found that inflammatory hindpaw pain in mouth, which was induced by injecting the complete Freund’s adjuvant (CFA) 2 days ago can be alleviated immediately after 2Hz 15mins EA treatment at contralateral forefoot acupoint LI4 through both mechanic and thermal behavior test, while sham acupoint group is not. The efficacy was observed to be more obvious after the second round of EA treatment on the following day. This analgesic effect is produced by applying EA to a site remote from the painful area. The present study provides a powerful experimental animal model that can be used for investigating the unique physiological mechanisms involved in acupuncture analgesia.

Keywords: remote electroacupuncture, distal EA, pain control, anti-inflammation

Procedia PDF Downloads 188

Authors: Dina Moheb Rashid Michael

Abstract:

A descriptive statistical analysis of the data showed that the most important factor evoking negative attitudes among teachers is student behavior. have been presented as useful models for understanding the risk factors and protective factors associated with the emergence of autistic traits. Although these "syndrome" forms of autism reach clinical thresholds, they appear to be distinctly different from the idiopathic or "non-syndrome" autism phenotype. Most teachers reported that kindergartens did not prepare them for the educational needs of children with autism, particularly in relation to non-verbal skills. The study is important and points the way for improving teacher inclusion education in Thailand. Inclusive education for students with autism is still in its infancy in Thailand. Although the number of autistic children in schools has increased significantly since the Thai government introduced the Education Regulations for Persons with Disabilities Act in 2008, there is a general lack of services for autistic students and their families. This quantitative study used the Teaching Skills and Readiness Scale for Students with Autism (APTSAS) to test the attitudes and readiness of 110 elementary school teachers when teaching students with autism in general education classrooms. To uncover the true nature of these co morbidities, it is necessary to expand the definition of autism to include the cognitive features of the disorder, and then apply this expanded conceptualization to examine patterns of autistic syndromes. This study used various established eye-tracking paradigms to assess the visual and attention performance of children with DS and FXS who meet the autism thresholds defined in the Social Communication Questionnaire. To study whether the autistic profiles of these children are associated with visual orientation difficulties ("sticky attention"), decreased social attention, and increased visual search performance, all of which are hallmarks of the idiopathic autistic child phenotype. Data will be collected from children with DS and FXS, aged 6 to 10 years, and two control groups matched for age and intellectual ability (i.e., children with idiopathic autism).In order to enable a comparison of visual attention profiles, cross-sectional analyzes of developmental trajectories are carried out. Significant differences in the visual-attentive processes underlying the presentation of autism in children with FXS and DS have been suggested, supporting the concept of syndrome specificity. The study provides insights into the complex heterogeneity associated with autism syndrome symptoms and autism itself, with clinical implications for the utility of autism intervention programs in DS and FXS populations.

Keywords: attitude, autism, teachers, sports activities, movement skills, motor skills

Procedia PDF Downloads 55

Authors: Mariam Atef Zakaria Faltas

Abstract:

A descriptive statistical analysis of the data showed that the most important factor evoking negative attitudes among teachers is student behavior. have been presented as useful models for understanding the risk factors and protective factors associated with the emergence of autistic traits. Although these "syndrome" forms of autism reach clinical thresholds, they appear to be distinctly different from the idiopathic or "non-syndrome" autism phenotype. Most teachers reported that kindergartens did not prepare them for the educational needs of children with autism, particularly in relation to non-verbal skills. The study is important and points the way for improving teacher inclusion education in Thailand. Inclusive education for students with autism is still in its infancy in Thailand. Although the number of autistic children in schools has increased significantly since the Thai government introduced the Education Regulations for Persons with Disabilities Act in 2008, there is a general lack of services for autistic students and their families. This quantitative study used the Teaching Skills and Readiness Scale for Students with Autism (APTSAS) to test the attitudes and readiness of 110 elementary school teachers when teaching students with autism in general education classrooms. To uncover the true nature of these co morbidities, it is necessary to expand the definition of autism to include the cognitive features of the disorder, and then apply this expanded conceptualization to examine patterns of autistic syndromes. This study used various established eye-tracking paradigms to assess the visual and attention performance of children with DS and FXS who meet the autism thresholds defined in the Social Communication Questionnaire. To study whether the autistic profiles of these children are associated with visual orientation difficulties ("sticky attention"), decreased social attention, and increased visual search performance, all of which are hallmarks of the idiopathic autistic child phenotype. Data will be collected from children with DS and FXS, aged 6 to 10 years, and two control groups matched for age and intellectual ability (i.e., children with idiopathic autism).In order to enable a comparison of visual attention profiles, cross-sectional analyzes of developmental trajectories are carried out. Significant differences in the visual-attentive processes underlying the presentation of autism in children with FXS and DS have been suggested, supporting the concept of syndrome specificity. The study provides insights into the complex heterogeneity associated with autism syndrome symptoms and autism itself, with clinical implications for the utility of autism intervention programs in DS and FXS populations.

Keywords: attitude, autism, teachers, sports activities, movement skills, motor skills

Procedia PDF Downloads 56

Authors: Randa Reda Luke Waheeb

Abstract:

A descriptive statistical analysis of the data showed that the most important factor evoking negative attitudes among teachers is student behavior. have been presented as useful models for understanding the risk factors and protective factors associated with the emergence of autistic traits. Although these "syndrome" forms of autism reach clinical thresholds, they appear to be distinctly different from the idiopathic or "non-syndrome" autism phenotype. Most teachers reported that kindergartens did not prepare them for the educational needs of children with autism, particularly in relation to non-verbal skills. The study is important and points the way for improving teacher inclusion education in Thailand. Inclusive education for students with autism is still in its infancy in Thailand. Although the number of autistic children in schools has increased significantly since the Thai government introduced the Education Regulations for Persons with Disabilities Act in 2008, there is a general lack of services for autistic students and their families. This quantitative study used the Teaching Skills and Readiness Scale for Students with Autism (APTSAS) to test the attitudes and readiness of 110 elementary school teachers when teaching students with autism in general education classrooms. To uncover the true nature of these co morbidities, it is necessary to expand the definition of autism to include the cognitive features of the disorder, and then apply this expanded conceptualization to examine patterns of autistic syndromes. This study used various established eye-tracking paradigms to assess the visual and attention performance of children with DS and FXS who meet the autism thresholds defined in the Social Communication Questionnaire. To study whether the autistic profiles of these children are associated with visual orientation difficulties ("sticky attention"), decreased social attention, and increased visual search performance, all of which are hallmarks of the idiopathic autistic child phenotype. Data will be collected from children with DS and FXS, aged 6 to 10 years, and two control groups matched for age and intellectual ability (i.e., children with idiopathic autism).In order to enable a comparison of visual attention profiles, cross-sectional analyzes of developmental trajectories are carried out. Significant differences in the visual-attentive processes underlying the presentation of autism in children with FXS and DS have been suggested, supporting the concept of syndrome specificity. The study provides insights into the complex heterogeneity associated with autism syndrome symptoms and autism itself, with clinical implications for the utility of autism intervention programs in DS and FXS populations.

Keywords: attitude, autism, teachers, sports activities, movement skills, motor skills

Procedia PDF Downloads 55

Authors: Amany Nosshy Fawzy George

Abstract:

A descriptive statistical analysis of the data showed that the most important factor evoking negative attitudes among teachers is student behavior. have been presented as useful models for understanding the risk factors and protective factors associated with the emergence of autistic traits. Although these "syndrome" forms of autism reach clinical thresholds, they appear to be distinctly different from the idiopathic or "non-syndrome" autism phenotype. Most teachers reported that kindergartens did not prepare them for the educational needs of children with autism, particularly in relation to non-verbal skills. The study is important and points the way for improving teacher inclusion education in Thailand. Inclusive education for students with autism is still in its infancy in Thailand. Although the number of autistic children in schools has increased significantly since the Thai government introduced the Education Regulations for Persons with Disabilities Act in 2008, there is a general lack of services for autistic students and their families. This quantitative study used the Teaching Skills and Readiness Scale for Students with Autism (APTSAS) to test the attitudes and readiness of 110 elementary school teachers when teaching students with autism in general education classrooms. To uncover the true nature of these co morbidities, it is necessary to expand the definition of autism to include the cognitive features of the disorder, and then apply this expanded conceptualization to examine patterns of autistic syndromes. This study used various established eye-tracking paradigms to assess the visual and attention performance of children with DS and FXS who meet the autism thresholds defined in the Social Communication Questionnaire. To study whether the autistic profiles of these children are associated with visual orientation difficulties ("sticky attention"), decreased social attention, and increased visual search performance, all of which are hallmarks of the idiopathic autistic child phenotype. Data will be collected from children with DS and FXS, aged 6 to 10 years, and two control groups matched for age and intellectual ability (i.e., children with idiopathic autism).In order to enable a comparison of visual attention profiles, cross-sectional analyzes of developmental trajectories are carried out. Significant differences in the visual-attentive processes underlying the presentation of autism in children with FXS and DS have been suggested, supporting the concept of syndrome specificity. The study provides insights into the complex heterogeneity associated with autism syndrome symptoms and autism itself, with clinical implications for the utility of autism intervention programs in DS and FXS populations.

Keywords: attitude, autism, teachers, sports activities, movement skills, motor skills

Procedia PDF Downloads 49

Authors: Abanoub Youssry Anwar Sadek

Abstract:

A descriptive statistical analysis of the data showed that the most important factor evoking negative attitudes among teachers is student behavior. have been presented as useful models for understanding the risk factors and protective factors associated with the emergence of autistic traits. Although these "syndrome" forms of autism reach clinical thresholds, they appear to be distinctly different from the idiopathic or "non-syndrome" autism phenotype. Most teachers reported that kindergartens did not prepare them for the educational needs of children with autism, particularly in relation to non-verbal skills. The study is important and points the way for improving teacher inclusion education in Thailand. Inclusive education for students with autism is still in its infancy in Thailand. Although the number of autistic children in schools has increased significantly since the Thai government introduced the Education Regulations for Persons with Disabilities Act in 2008, there is a general lack of services for autistic students and their families. This quantitative study used the Teaching Skills and Readiness Scale for Students with Autism (APTSAS) to test the attitudes and readiness of 110 elementary school teachers when teaching students with autism in general education classrooms. To uncover the true nature of these co morbidities, it is necessary to expand the definition of autism to include the cognitive features of the disorder, and then apply this expanded conceptualization to examine patterns of autistic syndromes. This study used various established eye-tracking paradigms to assess the visual and attention performance of children with DS and FXS who meet the autism thresholds defined in the Social Communication Questionnaire. To study whether the autistic profiles of these children are associated with visual orientation difficulties ("sticky attention"), decreased social attention, and increased visual search performance, all of which are hallmarks of the idiopathic autistic child phenotype. Data will be collected from children with DS and FXS, aged 6 to 10 years, and two control groups matched for age and intellectual ability (i.e., children with idiopathic autism).In order to enable a comparison of visual attention profiles, cross-sectional analyzes of developmental trajectories are carried out. Significant differences in the visual-attentive processes underlying the presentation of autism in children with FXS and DS have been suggested, supporting the concept of syndrome specificity. The study provides insights into the complex heterogeneity associated with autism syndrome symptoms and autism itself, with clinical implications for the utility of autism intervention programs in DS and FXS populations.

Keywords: attitude, autism, teachers, sports activities, movement skills, motor skills

Procedia PDF Downloads 42

Authors: Wassim Azmy Abdalla Ishak

Abstract:

A descriptive statistical analysis of the data showed that the most important factor evoking negative attitudes among teachers is student behavior. have been presented as useful models for understanding the risk factors and protective factors associated with the emergence of autistic traits. Although these "syndrome" forms of autism reach clinical thresholds, they appear to be distinctly different from the idiopathic or "non-syndrome" autism phenotype. Most teachers reported that kindergartens did not prepare them for the educational needs of children with autism, particularly in relation to non-verbal skills. The study is important and points the way for improving teacher inclusion education in Thailand. Inclusive education for students with autism is still in its infancy in Thailand. Although the number of autistic children in schools has increased significantly since the Thai government introduced the Education Regulations for Persons with Disabilities Act in 2008, there is a general lack of services for autistic students and their families. This quantitative study used the Teaching Skills and Readiness Scale for Students with Autism (APTSAS) to test the attitudes and readiness of 110 elementary school teachers when teaching students with autism in general education classrooms. To uncover the true nature of these co morbidities, it is necessary to expand the definition of autism to include the cognitive features of the disorder, and then apply this expanded conceptualization to examine patterns of autistic syndromes. This study used various established eye-tracking paradigms to assess the visual and attention performance of children with DS and FXS who meet the autism thresholds defined in the Social Communication Questionnaire. To study whether the autistic profiles of these children are associated with visual orientation difficulties ("sticky attention"), decreased social attention, and increased visual search performance, all of which are hallmarks of the idiopathic autistic child phenotype. Data will be collected from children with DS and FXS, aged 6 to 10 years, and two control groups matched for age and intellectual ability (i.e., children with idiopathic autism).In order to enable a comparison of visual attention profiles, cross-sectional analyzes of developmental trajectories are carried out. Significant differences in the visual-attentive processes underlying the presentation of autism in children with FXS and DS have been suggested, supporting the concept of syndrome specificity. The study provides insights into the complex heterogeneity associated with autism syndrome symptoms and autism itself, with clinical implications for the utility of autism intervention programs in DS and FXS populations

Keywords: attitude, autism, teachers, sports activities, movement skills, motor skills

Procedia PDF Downloads 36

Authors: Narges Arsanious Kamel Arsanious

Abstract:

A descriptive statistical analysis of the data showed that the most important factor evoking negative attitudes among teachers is student behavior. have been presented as useful models for understanding the risk factors and protective factors associated with the emergence of autistic traits. Although these "syndrome" forms of autism reach clinical thresholds, they appear to be distinctly different from the idiopathic or "non-syndrome" autism phenotype. Most teachers reported that kindergartens did not prepare them for the educational needs of children with autism, particularly in relation to non-verbal skills. The study is important and points the way for improving teacher inclusion education in Thailand. Inclusive education for students with autism is still in its infancy in Thailand. Although the number of autistic children in schools has increased significantly since the Thai government introduced the Education Regulations for Persons with Disabilities Act in 2008, there is a general lack of services for autistic students and their families. This quantitative study used the Teaching Skills and Readiness Scale for Students with Autism (APTSAS) to test the attitudes and readiness of 110 elementary school teachers when teaching students with autism in general education classrooms. To uncover the true nature of these co morbidities, it is necessary to expand the definition of autism to include the cognitive features of the disorder, and then apply this expanded conceptualization to examine patterns of autistic syndromes. This study used various established eye-tracking paradigms to assess the visual and attention performance of children with DS and FXS who meet the autism thresholds defined in the Social Communication Questionnaire. To study whether the autistic profiles of these children are associated with visual orientation difficulties ("sticky attention"), decreased social attention, and increased visual search performance, all of which are hallmarks of the idiopathic autistic child phenotype. Data will be collected from children with DS and FXS, aged 6 to 10 years, and two control groups matched for age and intellectual ability (i.e., children with idiopathic autism).In order to enable a comparison of visual attention profiles, cross-sectional analyzes of developmental trajectories are carried out. Significant differences in the visual-attentive processes underlying the presentation of autism in children with FXS and DS have been suggested, supporting the concept of syndrome specificity. The study provides insights into the complex heterogeneity associated with autism syndrome symptoms and autism itself, with clinical implications for the utility of autism intervention programs in DS and FXS populations.

Keywords: attitude, autism, teachers, sports activities, movement skills, motor skills

Procedia PDF Downloads 58

Authors: Narges Arsanious Kamel Arsanious

Abstract:

A descriptive statistical analysis of the data showed that the most important factor evoking negative attitudes among teachers is student behavior. It have been presented as useful models for understanding the risk factors and protective factors associated with the emergence of autistic traits. Although these ‘syndrome’ forms of autism reach clinical thresholds, they appear to be distinctly different from the idiopathic or ‘non-syndrome’ autism phenotype. Most teachers reported that kindergartens did not prepare them for the educational needs of children with autism, particularly in relation to non-verbal skills. The study is important and points the way for improving teacher inclusion education in Thailand. Inclusive education for students with autism is still in its infancy in Thailand. Although the number of autistic children in schools has increased significantly since the Thai government introduced the Education Regulations for Persons with Disabilities Act in 2008, there is a general lack of services for autistic students and their families. This quantitative study used the Teaching Skills and Readiness Scale for Students with Autism (APTSAS) to test the attitudes and readiness of 110 elementary school teachers when teaching students with autism in general education classrooms. To uncover the true nature of these co morbidities, it is necessary to expand the definition of autism to include the cognitive features of the disorder, and then apply this expanded conceptualization to examine patterns of autistic syndromes. This study used various established eye-tracking paradigms to assess the visual and attention performance of children with DS and FXS who meet the autism thresholds defined in the Social Communication Questionnaire. To study whether the autistic profiles of these children are associated with visual orientation difficulties (sticky attention), decreased social attention, and increased visual search performance, all of which are hallmarks of the idiopathic autistic child phenotype. Data will be collected from children with DS and FXS, aged 6 to 10 years, and two control groups matched for age and intellectual ability (i.e., children with idiopathic autism). In order to enable a comparison of visual attention profiles, cross-sectional analyzes of developmental trajectories are carried out. Significant differences in the visual-attentive processes underlying the presentation of autism in children with FXS and DS have been suggested, supporting the concept of syndrome specificity. The study provides insights into the complex heterogeneity associated with autism syndrome symptoms and autism itself, with clinical implications for the utility of autism intervention programs in DS and FXS populations.

Keywords: attitude, autism, teachers, sports activities, movement skills, motor skills

Procedia PDF Downloads 42

Authors: Liu Xiaohan

Abstract:

Epstein–Barr virus (EBV) is a human herpesvirus and is closely related to many malignancies of lymphocyte and epithelial origins, such as gastric cancer, Burkitt’s lymphoma, and nasopharyngeal carcinoma (NPC). NPC is a malignant epithelial tumor which is 100% associated with EBV latent infection. Most of the NPC cases are densely populated in southern China, especially in Guangdong and Hong Kong. To our knowledge, overexpression of pro-inflammatory cytokines may result in a loss of balance of the immune system and cause damage to human bodies. Interleukin-6 (IL6) is a pro-inflammatory cytokine which plays an important role in tumor progression. In addition, gene expression is regulated by both transcriptional and post-transcriptional pathways, while post-transcriptional regulation is an important mechanism to modulate the mature mRNA level in mammalian cells. AU-rich element binding factor 1 (AUF1)/heterogeneous nuclear RNP D (hnRNP D) is known for its function in destabilizing mRNAs, including cytokines and cell cycle regulators. Previous studies have found that overexpression of hnRNP D would lead to tumorigenesis. In this project, our aim is to determine the role played by hnRNP D in EBV-infected cells and how our anti-EBV agents can affect the function of hnRNP D. The results of this study will provide a new insight into how the pro-inflammatory cytokine expression can be regulated by EBV.

Keywords: interleukin 6 (IL6), epstein-barr virus (EBV), nasopharyngeal carcinoma (NPC, epstein-barr nuclear antigen-1 (EBNA1)

Procedia PDF Downloads 62

Authors: S. Ibrahim, D. Salilew-Wondim, M. Hoelker, C. Looft, E. Tholen, C. Grosse-Brinkhaus, K. Schellander, C. Neuhoff, D. Tesfaye

Abstract:

Bovine endometrial cells appear to have a key role in innate immune defense of the female genital tract. A better understanding of molecular changes in microRNAs (miRNAs) and their target genes expression may identify reliable prognostic indicators for cows that will resolve inflammation and resume cyclicity. In the current study, we hypothesized that let-7 miRNAs family has a primary role in the innate immune defence of the endometrium tissue against bacterial infection, which is partly achieved via regulating mRNA stability of pro-inflammatory cytokines at the post-transcriptional level. Therefore, we conducted two experiments. In the first experiment, primary bovine endometrial cells were challenged with clinical (3.0 μg/ml) and sub-clinical (0.5 μg/ml) doses of lipopolysaccharide (LPS) for 24h. In the 2nd experiment, we have investigated the potential role of let-7 miRNAs (let-7a and let-7f) using gain and loss of function approaches. Additionally, tumor necrosis factor alpha (TNFα), transforming growth factor beta 1 induced transcript 1 (TGFB1I1) and serum deprivation response (SDPR) genes were validated using reporter assay. Here we addressed for the first time that let-7 miRNAs have a precise role in bovine endometrium, where LPS dysregulated let-7 miRNAs family expression was associated with an increased pro-inflammatory cytokine level by directly/indirectly targeting the TNFα, interleukin 6 (IL6), nuclear factor kappa-light-chain enhancer of activated B cells (NFκB), TGFβ1I1 and SDPR genes. To our knowledge, this is the first study showing that TNFα, TGFβ1I1 and SDPR were identified and validated as novel let-7 miRNAs targets and could have a distinct role in inflammatory immune response of LPS challenged bovine endometrial cells. Our data represent a new finding by which uterine homeostasis is maintained through functional regulation of let-7a by down-regulation of pro-inflammatory cytokines expression (TNFα and IL6) at the mRNA and protein levels. These findings suggest that LPS serves as a negative regulator of let-7 miRNAs expression and provides a mechanism for the persistent pro-inflammatory phenotype, which is a hallmark of bovine subclinical endometritis.

Keywords: bovine endometrial cells, let-7, lipopolysaccharide, pro-inflammatory cytokines

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Authors: Corina Muscurel, Irina Stoian, Laura Gaman, Valeriu Atanasiu

Abstract:

Chronic inflammation predisposes cells to neoplastic transformation and is associated with angiogenesis. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) give rise to anti-inflammatory metabolites and decrease some inflammatory cytokines. The aim of the study was to analyze the effect of n-3 PUFAs intake on patients with tumors in early-stage (without regional or distant metastasis). There were two groups of patients: one group with colon tumors and one group with lung tumors. All patients took for 60 days daily supplements from fish-oil containing 600 mg eicosapentaenoic acid and 400 mg docosahexaenoic acid. The plasma markers were evaluated before and after PUFAs intake: ceruloplasmin (using p-phenylenediamine oxidase method), plasma total thiol groups (using dithiobis-nitrobenzoic acid method) and CEA (carcinoembryonic antigen using electrochemiluminescent immunoassay). The results reflect ceruloplasmin decrease (p < 0.05), plasma total thiol groups increase (not statistically significant) and CEA decrease (p < 0.05) after n-3 PUFAs intake. Conclusions: n-3 PUFAs intake is favorable in premalignant lesions or in early tumor stage and dietary fish-oil has anti-inflammatory effects and can contribute to reduce cancer progression.

Keywords: cancer, fish-oil, inflammation, n-3 polyunsaturated fatty acids

Procedia PDF Downloads 136

Authors: Jyoti Singh, Ranju Bansal

Abstract:

Fighting pain and inflammation is a common problem faced by physicians while dealing with a wide variety of diseases. Since ancient time nonsteroidal anti-inflammatory agents (NSAIDs) and opioids have been the cornerstone of treatment therapy, however, the usefulness of both these classes is limited due to severe side effects. NSAIDs, which are mainly used to treat mild to moderate inflammatory pain, induce gastric irritation and nephrotoxicity whereas opioids show an array of adverse reactions such as respiratory depression, sedation, and constipation. Moreover, repeated administration of these drugs induces tolerance to the analgesic effects and physical dependence. Further discovery of selective COX-2 inhibitors (coxibs) suggested safety without any ulcerogenic side effects; however, long-term use of these drugs resulted in kidney and hepatic toxicity along with an increased risk of secondary cardiovascular effects. The basic approaches towards inflammation and pain treatment are constantly changing, and researchers are continuously trying to develop safer and effective anti-inflammatory drug candidates for the treatment of different inflammatory conditions such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, psoriasis and multiple sclerosis. Synthetic 3(2H)-pyridazinones constitute an important scaffold for drug discovery. Structure-activity relationship studies on pyridazinones have shown that attachment of a lactam at N-2 of the pyridazinone ring through a methylene spacer results in significantly increased anti-inflammatory and analgesic properties of the derivatives. Further introduction of the heterocyclic ring at lactam nitrogen results in improvement of biological activities. Keeping in mind these SAR studies, a new series of compounds were synthesized as shown in scheme 1 and investigated for anti-inflammatory, analgesic, anti-platelet activities and docking studies. The structures of newly synthesized compounds have been established by various spectroscopic techniques. All the synthesized pyridazinone derivatives exhibited potent anti-inflammatory and analgesic activity. Homoveratryl substituted derivative was found to possess highest anti-inflammatory and analgesic activity displaying 73.60 % inhibition of edema at 40 mg/kg with no ulcerogenic activity when compared to standard drugs indomethacin. Moreover, 2-substituted-4-benzo[d][1,3]dioxole-6-phenylpyridazin-3(2H)-ones derivatives did not produce significant changes in bleeding time and emerged as safe agents. Molecular docking studies also illustrated good binding interactions at the active site of the cyclooxygenase-2 (hCox-2) enzyme.

Keywords: anti-inflammatory, analgesic, pyridazin-3(2H)-one, selective COX-2 inhibitors

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Authors: Abdelkrim Khadir, Sina Kavalakatt, Preethi Cherian, Ali Tiss

Abstract:

Soluble epoxide hydrolase (sEH) is an emerging therapeutic target in several chronic states that have inflammation as a common underlying cause such as immunometabolic diseases. Indeed, sEH is known to play a pro-inflammatory role by metabolizing anti-inflammatory, epoxyeicosatrienoic acids (EETs) to pro-inflammatory diols. Recently, it was shown sEH to be linked to diet and microbiota interaction in rat models of obesity. Nevertheless, the functional contribution of sEH and its anti-inflammatory substrates EETs in obesity remain poorly understood. In the current study, we compared the expression pattern of sEH between lean and obese nondiabetic human subjects using subcutaneous adipose tissue (SAT) and peripheral blood mononuclear cells (PBMCs). Using RT-PCR, western blot and immunofluorescence confocal microscopy, we show here that the level of sEH mRNA and protein to be significantly increased in obese subjects with concomitant increase in endoplasmic reticulum (ER) stress components (GRP78 and ATF6α) and inflammatory markers (TNF-α, IL-6) when compared to lean controls. The observation that sEH was overexpressed in obese subjects’ prompt us to investigate whether physical exercise could reduce its expression. In this study, we report here 3-months supervised physical exercise significantly attenuated the expression of sEH in both the SAT and PBMCs, with a parallel decrease in the expression of ER stress markers along with attenuated inflammatory response. On the other hand, homocysteine, a sulfur containing amino acid deriving from the essential amino acid methionine was shown to be directly associated with insulin resistance. When 3T3-L1 preadipocytes cells were treated with homocysteine our results show increased sEH levels along with ER stress markers. Collectively, our data suggest that sEH upregulation is strongly linked to ER stress in adiposity and that physical exercise modulates its expression. This gives further evidence that exercise might be useful as a strategy for managing obesity and preventing its associated complications.

Keywords: obesity, adipose tissue, epoxide hydrolase, ER stress

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Authors: Benedict Ofori, Kwabena Sarpong, Stephen Antwi

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Background: Medicinal plants are utilized all around the world and are becoming increasingly important economically. The WHO notes that ‘inappropriate use of traditional medicines or practices can have negative or dangerous effects and that future research is needed to ascertain the efficacy and safety of such practices and medicinal plants used by traditional medicine systems. The poor around the world have limited access to palliative care or pain relief. Pharmacologists have been focused on developing safe and effective anti-inflammatory drugs. Most of the issues related to their use have been linked to the fact that numerous traditional and herbal treatments are classified in different nations as meals or dietary supplements. As a result, there is no need for evidence of the quality, efficacy, or safety of these herbal formulations before they are marketed. The fact that access to drugs meant for pain relief is limited in low-income countries means advanced studies should be done on home drugs meant for inflammation to close the gap. Methods: The ethanolic extracts of the plant were screened for the presence of 10 phytochemicals. The Pierce BCA Protein Assay Kit was used for the determination of the protein concentration of the egg white. The rats were randomly selected and put in 6 groups. The egg white was sub-plantar injected into the right-hand paws of the rats to induce inflammation. The animals were treated with the three plant extracts obtained from the root bark, stem, and leaves of the plant. The control groups were treated with normal saline, while the standard groups were treated with standard drugs indomethacin and celecoxib. Plethysmometer was used to measure the change in paw volume of the animals over the course of the experiment. Results: The results of the phytochemical screening revealed the presence of reducing sugars and saponins. Alkaloids were present in only R.L.S (1:1:1), and phytosterols were found in R.L(1:1) and R.L.S (1:1:1). The estimated protein concentration was found to be 103.75 mg/ml. The control group had an observable increase in paw volume, which indicated that inflammation was induced during the 5 hours. The increase in paw volume for the control group peaked at the 1st hour and decreased gradually throughout the experiment, with minimal changes in the paw volumes. The 2nd and 3rd groups were treated with 20 mg/kg of indomethacin and celecoxib. The anti-inflammatory activities of indomethacin and celecoxib were calculated to be 21.4% and 4.28%, respectively. The remaining 3 groups were treated with 2 dose levels of 200mg/kg plant extracts. R.L.S, R.L, and S.R.L had anti-inflammatory activities of 22.3%, 8.2%, and 12.07%, respectively. Conclusions: Egg albumin-induced paw model in rats can be used to evaluate the anti-inflammatory activity of herbs that might have potential anti-inflammatory activity. Herbal medications have potential anti-inflammatory activities and can be used to manage various inflammatory conditions if their efficacy and side effects are well studied. The three extracts all possessed anti-inflammatory activity, with R.L.S having the highest anti-inflammatory activity.

Keywords: inflammation, capparis erythrocarpos, anti-inflammatory activity, herbal medicine, paw volume, egg albumin

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Authors: Karolina Siejka, Monika Piekarska, Monika Zbroja, Weronika Cyranka, Maryla Kuczynska, Magdalena Grzegorczyk, Malgorzata Nowakowska, Agnieszka Brodzisz, Magdalena Maria Wozniak

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Crohn’s disease is one of chronic inflammatory bowel diseases. It is increasing in prevalence worldwide, especially with young people. The disease usually occurs in the second to the fourth decade of life. Traditionally is diagnosed by clinical indicates, endoscopic, and histological findings. Magnetic Resonance Enterography (MRE) can demonstrate mural and extramural inflammatory signs and complications, which make it a valuable diagnostic modality. The study included 76 adults and 36 children diagnosed with Crohn’s disease. Each patient underwent MRE with intravenous administration of a contrast agent. All the studies were performed using Siemens Aera 1.5T scanner according to a local study protocol. Whenever applicable, MR Enterography findings were verified with endoscopy. Forty adults and all 36 children had an active phase of Crohn’s disease; five adults had a chronic phase of the disease; one adult had both chronic and active inflammatory features. Thirty adults have no sings of pathology. In both adult and pediatric groups the most commonly observed manifestation of active disease was thickened edematous ileum wall (26 adults and 36 children). Adults had Bauhin’s valve edema in 58% cases (n=23) and mesenteric changes in 34% cases (n=9). To compare, 32 children had Bauhin’s valve edema (89%) and, in 23 cases, was found inflammatory infiltration of the peri-intestinal fat (64%). The involvement of the large intestine was more common among children (100%). Complications of Crohn’s disease were found commonly in adults (40% of adults, 22% of children). There were observed 18 fistulas (14 adults, four children) and six abscesses (2 adults, four children). MRE is a reliable method in the evaluation of Crohn’s disease activity, especially of its complications. The lack of radiations makes MRE well-tolerated modality, which can be often repeated, particularly in young patients. The disease had different medical sings depending on age – children often had a more active inflammatory process, but there were more complications in the adult group.

Keywords: Crohn's disease, diagnostics, inflammatory bowel disease, magnetic resonance enterography, MRE

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Authors: S. Nasri, G. H. Amin, A. Azimi

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The use of herbs to treat disease is accompanied with the history of human life. This research is aimed to study the anti-inflammatory and antinociceptive effects of hydroalcoholic extract of aerial parts of "Tanacetum balsamita balsamita". In the experimental studies 144 male mice are used. In the inflammatory test, animals were divided into six groups: Control, positive control (receiving Dexamethason at dose of 15mg/kg), and four experimental groups receiving Tanacetum balsamita balsamita hydroalcoholic extract at doses of 25, 50, 100 and 200mg/kg. Xylene was used to induce inflammation. Formalin was used to study the nociceptive effects. Animals were divided into six groups: control group, positive control group (receiving morphine) and four experimental groups receiving Tanacetum balsamita balsamita (Tb.) hydroalcoholic extract at doses of 25, 50, 100 and 200mg/kg. I.p. injection of drugs or normal saline was performed 30 minutes before test. The data were analyzed by using one way Variance analysis and Tukey post-test. Aerial parts of Tanacetum balsamita balsamita hydroalcoholic extract decreased significantly inflammatory at dose of 200mg/kg (P<0/001) and caused a significant decrease and alleviated the nociception in both first and second phases at doses of 200mg/kg (p<0/001) and 100mg/kg (P<0/05). Tanacetum balsamita balsamita extract has the anti-inflammatory and anti-nociceptive effects which seems to be related with flavonoids especially Quercetin.

Keywords: inflammation, nociception, hydroalcoholic extract, aerial parts of Tanacetum balsamita balsamita L.

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Authors: Shweta Sinha, Mukesh Doble, Manju S. L.

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Pyrazole scaffold is an important group of compound in heterocyclic chemistry and is found to possess numerous uses in chemistry. Pyrazole derivatives are also known to possess important biological activities including antitumor, antimicrobial, antiviral, antifungal, anticancer and anti-inflammatory. Inflammation is associated with pain, allergy and asthma. Leukotrienes are mediators of various inflammatory and allergic disorders. 5-Lipoxygenase (5-LOX) is an important enzyme involved in the biosynthesis of leukotrienes and metabolism of arachidonic acid (AA) and thus targeted for anti-inflammation. In vitro inhibitory activity of pyrazol-3-yl thiazole 4-carboxylic acid derivatives is tested against enzyme 5-LOX. Most of these compounds exhibit good inhibitory activity against this enzyme. Binding mode study of these compounds is determined by computational tool. Further experiments are being done to understand the mechanism of action of these compounds in inhibiting this enzyme. To conclude, these compounds appear to be a promising target in drug design against 5-LOX.

Keywords: inflammation, inhibition, 5-lipoxygenase, pyrazole

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Authors: Tauseef Ahmad, Muhammad Ishaq, Mathew Eapen, Ahyoung Park, Sam Karpiniec, Vanni Caruso, Rajaraman Eri

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Fucoidans are complex, fucose-rich sulfated polymers discovered in brown seaweeds. Fucoidans are popular around the world, particularly in the nutraceutical and pharmaceutical industries, due to their promising medicinal properties. Fucoidans have been shown to have a variety of biological activities, including anti-inflammatory effects. They are known to inhibit inflammatory processes through a variety of mechanisms, including enzyme inhibition and selectin blockade. Inflammation is a part of the complicated biological response of living systems to damaging stimuli, and it plays a role in the pathogenesis of a variety of disorders, including arthritis, inflammatory bowel disease, cancer, and allergies. In the current investigation, various fucoidan extracts from Undaria pinnatifida, Fucus vesiculosus, Macrocystis pyrifera, Ascophyllum nodosum, and Laminaria japonica were assessed for inhibition of pro-inflammatory cytokine production (TNF-α, IL-1β, and IL-6) in LPS induced human macrophage cell line (THP-1) and human peripheral blood mononuclear cells (PBMCs). Furthermore, we also sought to catalogue these extracts based on their anti-inflammatory effects in the current in-vitro cell model. Materials and Methods: To assess the cytotoxicity of fucoidan extracts, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5, -diphenyltetrazolium bromide) cell viability assay was performed. Furthermore, a dose-response for fucoidan extracts was performed in LPS induced THP-1 cells and PBMCs after pre-treatment for 24 hours, and levels of TNF-α, IL-1β, and IL-6 cytokines were measured using Enzyme-Linked Immunosorbent Assay (ELISA). Results: The MTT cell viability assay demonstrated that fucoidan extracts exhibited no evidence of cytotoxicity in THP-1 cells or PBMCs after 48 hours of incubation. The results of the sandwich ELISA revealed that all fucoidan extracts suppressed cytokine production in LPS-stimulated PBMCs and human THP-1 cells in a dose-dependent manner. Notably, at lower concentrations, the lower molecular fucoidan (5-30 kDa) extract from Macrocystis pyrifera was a highly efficient inhibitor of pro-inflammatory cytokines. Fucoidan extracts from all species including Undaria pinnatifida, Fucus vesiculosus, Macrocystis pyrifera, Ascophyllum nodosum, and Laminaria japonica exhibited significant anti-inflammatory effects. These findings on several fucoidan extracts provide insight into strategies for improving their efficacy against inflammation-related diseases. Conclusion: In the current research, we have successfully catalogued several fucoidan extracts based on their efficiency in LPS-induced macrophages and PBMCs in downregulating the key pro-inflammatory cytokines (TNF-, IL-1 and IL-6), which are prospective targets in human inflammatory illnesses. Further research would provide more information on the mechanism of action, allowing it to be tested for therapeutic purposes as an anti-inflammatory medication.

Keywords: fucoidan, PBMCs, THP-1, TNF-α, IL-1β, IL-6, inflammation

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Authors: Hana Al-Baghaoi, Kumar Shiva Gubbiyappa, Mayuren Candasamy, Kiruthiga Perumal Vijayaraman

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Acne is a chronic inflammatory disease of the sebaceous glands characterized by areas of skin with seborrhea, comedones, papules, pustules, nodules, and possibly scarring. Propionibacterium acnes (P. acnes), plays a key role in the pathogenesis of acne. Their colonization and proliferation trigger the host’s inflammatory response leading to the production of pro-inflammatory cytokines such as interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α). The usage of honey and natural compounds to treat skin ailments has strong support in the current trend of drug discovery. The present study was carried out evaluate antimicrobial and anti-inflammatory potential of Doani Sidr honey and its fractions against P. acnes and to screen madecassoside alone and in combination with fractions of honey. The broth dilution method was used to assess the antibacterial activity. Also, ultra structural changes in cell morphology were studied before and after exposure to Sidr honey using transmission electron microscopy (TEM). The three non-toxic concentrations of the samples were investigated for suppression of cytokines IL 8 and TNF α by testing the cell supernatants in the co-culture of the human peripheral blood mononuclear cells (hPBMCs) heat killed P. acnes using enzyme immunoassay kits (ELISA). Results obtained was evaluated by statistical analysis using Graph Pad Prism 5 software. The Doani Sidr honey and polysaccharide fractions were able to inhibit the growth of P. acnes with a noteworthy minimum inhibitory concentration (MIC) value of 18% (w/v) and 29% (w/v), respectively. The proximity of MIC and MBC values indicates that Doani Sidr honey had bactericidal effect against P. acnes which is confirmed by TEM analysis. TEM images of P. acnes after treatment with Doani Sidr honey showed completely physical membrane damage and lysis of cells; whereas non honey treated cells (control) did not show any damage. In addition, Doani Sidr honey and its fractions significantly inhibited (> 90%) of secretion of pro-inflammatory cytokines like TNF α and IL 8 by hPBMCs pretreated with heat-killed P. acnes. However, no significant inhibition was detected for madecassoside at its highest concentration tested. Our results suggested that Doani Sidr honey possesses both antimicrobial and anti-inflammatory effects against P. acnes and can possibly be used as therapeutic agents for acne. Furthermore, polysaccharide fraction derived from Doani Sidr honey showed potent inhibitory effect toward P. acnes. Hence, we hypothesize that fraction prepared from Sidr honey might be contributing to the antimicrobial and anti-inflammatory activity. Therefore, this polysaccharide fraction of Doani Sidr honey needs to be further explored and characterized for various phytochemicals which are contributing to antimicrobial and anti-inflammatory properties.

Keywords: Doani sidr honey, Propionibacterium acnes, IL-8, TNF alpha

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Authors: Agustyas Tjiptaningrum, Intanri Kurniati, Fadilah Fadilah, Linda Erlina, Tiwuk Susantiningsih

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Coronavirus disease-19 (COVID-19) is still one of the health problems. It can be a severe condition that is caused by a cytokine storm. In a cytokine storm, several proinflammatory cytokines are released massively. It destroys epithelial cells, and subsequently, it can cause death. The anti-inflammatory agent can be used to decrease the number of severe Covid-19 conditions. Melaleuca cajuputi is a plant that has antiviral, antibiotic, antioxidant, and anti-inflammatory activities. This study was carried out to analyze the prediction mechanism of the M. cajuputi extract from Lampung, Indonesia, as an anti-inflammatory agent for COVID-19. This study constructed a database of protein host target that was involved in the inflammation process of COVID-19 using data retrieval from GeneCards with the keyword “SARS-CoV2”, “inflammation,” “cytokine storm,” and “acute respiratory distress syndrome.” Subsequent protein-protein interaction was generated by using Cytoscape version 3.9.1. It can predict the significant target protein. Then the analysis of the Gene Ontology (GO) and KEGG pathways was conducted to generate the genes and components that play a role in COVID-19. The result of this study was 30 nodes representing significant proteins, namely NF-κβ, IL-6, IL-6R, IL-2RA, IL-2, IFN2, C3, TRAF6, IFNAR1, and DOX58. From the KEGG pathway, we obtained the result that NF-κβ has a role in the production of proinflammatory cytokines, which play a role in the COVID-19 cytokine storm. It is an important factor for macrophage transcription; therefore, it will induce inflammatory gene expression that encodes proinflammatory cytokines such as IL-6, TNF-α, and IL-1β. In conclusion, the blocking of NF-κβ is the prediction mechanism of the M. cajuputi extract as an anti-inflammation agent for COVID-19.

Keywords: antiinflammation, COVID-19, cytokine storm, NF-κβ, M. cajuputi

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Authors: Deepak Mohan, Sushma Sharma

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Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are a group of widely used drugs for the treatment of rheumatoid diseases and to relieve pain and inflammation due to their analgesic anti-pyretic and anti-inflammatory properties. The therapeutic and many of the toxic effects of NSAIDs result from reversible inhibition of enzymes in the cyclooxygenase (COX) group. In the present investigation the effect of the drug on the concentration of lipids, and on the activity of the enzymes i.e. acid and alkaline phosphatase, GOT, GPT and lipid peroxidase were studied. There was a significant enhancement in the activities of both acid and alkaline phosphatase after 21 days of treatment. Proportionate increase in the MDA contents was observed after different days of diclofenac treatment. Cellular damage in the liver resulted in decrease in the activity of both GOT (Glutamate oxaloacetate transaminase) and GPT (Glutamate pyruvate transaminase) in both low and high dose groups. Significant decrease in the liver contents was also observed in both dose groups.

Keywords: anti-inflammatory, cyclooxygenase, glutamate oxaloacetate transaminase, malondialdehyde

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Authors: Husham Bayazed

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A growing number of studies indicate that atherosclerotic coronary artery disease (CAD) has a complex pathogenesis that extends beyond cholesterol intimal infiltration. The atherosclerosis process may involve an immune micro-environmental condition driven by local activation of the adaptive and innate immunity arrays, resulting in the formation of atherosclerotic plaques. Therefore, despite the wide usage of lipid-lowering agents, these devastating coronary diseases are not averted either at primary or secondary prevention levels. Many trials have recently shown an interest in the immune targeting of the inflammatory process of atherosclerotic plaques, with the promised improvement in atherosclerotic cardiovascular disease outcomes. This recently includes the immune-modulatory drug “Canakinumab” as an anti-interleukin-1 beta monoclonal antibody in addition to "Colchicine,” which's established as a broad-effect drug in the management of other inflammatory conditions. Recent trials and studies highlight the importance of inflammation and immune reactions in the pathogenesis of atherosclerosis and plaque formation. This provides an insight to discuss and extend the therapies from old lipid-lowering drugs (statins) to anti-inflammatory drugs (colchicine) and new targeted immune-modulatory therapies like inhibitors of IL-1 beta (canakinumab) currently under investigation.

Keywords: atherosclerotic plagues, immune microenvironment, lipid-lowering agents, and immunomodulatory drugs

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Authors: Sina Mahdavi

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Multiple sclerosis (MS) is a progressive inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially human immunodeficiency virus (HIV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on human HIV infection in MS disease progression. In this study, the keywords "Multiple sclerosis", "Human immunodeficiency virus ", and "Central nervous system" in the databases PubMed, and Google Scholar between 2017 and 2022 were searched and 15 articles were chosen, studied, and analyzed. Revealed histologic signs of "MS-like illness" in the setting of HIV, which comprised widespread demyelination with reactive astrocytes, foamy macrophages, and perivascular infiltration with inflammatory cells, all of which are compatible with MS lesions. Human immunodeficiency virus causes dysfunction of the immune system, especially characterized by hypergammaglobulinemia and chronic activation of B cells. Activation of B cells leads to increased synthesis of immunoglobulin and finally to an excess of free light chains. Free light chains may be involved in autoimmune responses against neurons. There is a high expression of HIV during the course of MS, which indicates the relationship between HIV and MS, that this virus can play a role in the development of MS by creating an inflammatory state. Therefore, measures to modulate the expression of HIV may be effective in reducing inflammatory processes in demyelinated areas of MS patients.

Keywords: multiple sclerosis, human immunodeficiency virus, central nervous system, autoimmunity

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Authors: Sourav Ghosh, Antony Gomes

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Since 1894 anti-snake venom serum (ASVS) is the only available treatment against snake envenomation, although there are many side effects and limitations. The need for a supportive treatment was felt for a long time to overcome the side effects and limitations of ASVS. Andrographolide conjugated with gold nanoparticle (A-GNP) has been found to antagonize viper venom-induced local damages. The present study was aimed to study the protective efficacy of A-GNP against Viper venom-induced inflammatory response and organ toxicity in animal model. Ethical clearance was obtained from animal experiments. Physico-chemical characterization of A-GNP was done by DLS (diameter and zeta potential), FE-SEM and XRD. Swiss albino male mice were divided into 4 groups: Gr.1-Sham control, Gr.2- Russell’s Viper venom (RVV) control, Gr.3- andrographolide treated and Gr.4- A-GNP treated. The 1/5th minimum lethal dose of RVV (500µg/kg, s.c.) was induced in animals of group 2, 3 & 4 animals, followed by treatment with andrographolide (100mg/kg, i.p.) and A-GNP (100mg/kg, i.v.) in group 3 & 4 animals, respectively. Blood was collected after 18 h, serum was prepared, and inflammatory markers (IL 1β, 6, 17a, 10, TNF α) and biochemical markers (AST, ACP, LDH, urea, creatinine) were assessed. Values were expressed as mean±SEM (n=4), one way ANOVA was done, P<0.05 was considered as statistically significant. DLS size showed the hydrodynamic diameter of A-GNP to be 230-260nm with polydispersity index of 0.103 and zeta potential was -18.32mV. XRD data confirmed the presence of crystalline gold in A-GNP, and FESEM indicated the presence of nearly spherical particle with size18-24nm.Treatment with A-GNP significantly decreased viper venom-induced proinflammatory markers (IL 1β, 6, 17, TNF α) increased anti-inflammatory markers (IL 10) and decreased organ toxicity markers (AST, ACP, LDH, urea, creatinine) in animal model. Venom neutralization efficacy of A-GNP was > andrographolide, which confirmed the increased efficacy of andrographolide after gold nanoparticle conjugation. Venom neutralization by A-GNP was due to anti-oxidant/anti-inflammatory activity of andrographolide, which showed increased efficacy after gold nanoparticle tagging. Thus, A-GNP may serve as a supportive therapy in snake-bite (against inflammatory response and organ toxicity) subject to further detail studies.

Keywords: andrographolide, gold nanoparticle, inflammatory response, organ toxicity, snake venom, snake venom neutralization, viper venom

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Authors: Naim Izet Kajtazi

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Context: Frequently, the cause of raised intracranial pressure remains unresolved and rarely is related to spinal tumors, moreover less to spinal medulloblastoma without primary brain focus. Process: An 18-year-old woman had a 3-month history of headaches and impaired vision. Neurological examination revealed bilateral sixth cranial nerve palsies with bilateral papilloedema of grade III. No focal brain or spine lesion was found on imaging. Consecutive lumbar punctures showed high opening pressure and subsequent increasing protein level. The meningeal biopsy was negative. At one point, she developed an increasing headache, vomiting and back pain. Spine MRI showed diffuse nodular leptomeningeal enhancement with the largest nodule at T6–T7. Malignant cells were detected in cerebrospinal fluid. She underwent laminectomy with excisional biopsy, and pathology showed medulloblastoma WHO grade IV. Outcome: She was treated with chemotherapy and craniospinal irradiation and made a good recovery. Relevance: Primary spinal leptomeningeal medulloblastoma is extremely rare, especially without primary brain focus, but may cause increased intracranial pressure, even in the early microscopic phases, and it should be considered in the differential diagnosis if conventional and aggressive treatment of idiopathic intracranial hypertension fails. We assume that arachnoiditis from tumor seeding caused increased intracranial pressure. Appropriate neurosurgical intervention and surgical biopsy are mandated if a suspicious lesion is detected. Consider proper rescreening of the whole neuroaxis in refractory cases of intracranial hypertension.

Keywords: CNS infection, IIH, headache, primary spinal leptomeningeal medulloblastoma

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Authors: Ashit Syngle, Inderjit Verma, Pawan Krishan

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Therapeutic approaches used previously relied on disease-modifying antirheumatic drugs (DMARDs) that had only partial clinical benefit and were associated with significant toxicity. Spironolactone, an oral aldosterone antagonist, suppresses inflammatory mediators. Clinical efficacy of spironolactone compared with placebo in patients with active psoriatic arthritis despite treatment with prior traditional DMARDs. In the 24-week, placebo-controlled study patients (n=31) were randomized to placebo and spironolactone (2 m/kg/day). Patients on background concurrent DMARDs continued stable doses (methotrexate, leflunomide, and/or sulfasalazine). Primary outcome measures were the assessment of disease activity measures i.e. 28-joint disease activity score (DAS28) and diseases activity in psoriatic arthritis (DAPSA) at week 24. The key secondary endpoint was change from baseline in Health Assessment Questionnaire–Disability Index (HAQ-DI) at week 24. Additional efficacy outcome measures at week 24 included improvements in the markers of inflammation (ESR and CRP) and pro-inflammatory cytokines TNF-α, IL-6 and IL-1. At week 24, spironolactone significantly reduced disease activity measure DAS-28 (p<0.001) and DAPSA (p=0.001) compared with placebo. Significant improvements in key secondary measures HAQ-DI (disability index) were evident with spironolactone (p=0.02) versus placebo. After week 24, there was significant reduction in pro-inflammatory cytokines level TNF-α, IL-6 (p<0.01) as compared with placebo group. However, there was no significant improvement in IL-1 in both treatment and placebo groups. There were minor side effects which did not mandate stopping of spironolactone. No change in any biochemical profile was noted after spironolactone treatment. Spironolactone was effective in the treatment of PsA, improving disease activity, physical function and suppressing the level of pro-inflammatory cytokines. Spironolactone demonstrated an acceptable safety profile and was well tolerated.

Keywords: spironolactone, inflammation, inflammatory cytokine, psoriatic arthritis

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