Search results for: inflammatory mediators

Authors: Anca Dinischiotu, Sorina Nicoleta Voicu

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Silica nanoparticles (SiO2-NPs) are widely used in consumer products such as paints, plastics, insulation materials, tires, concrete production, as well as in gene delivery systems and imaging procedures. Environmental human exposure to them occurs during utilization of these products, in a time-dependent manner, the uptake being by topic and inhalation route especially. SiO2-NPs enter cells and induce membrane damage, oxidative stress and inflammatory reactions in a concentration-dependent manner. In this study, MRC-5 cells (human fetal lung fibroblasts) were exposed to amorphous SiO2-NPs at a dose of 62.5 μg/ml for 24, 48 and 72 hours. The size distribution of NPs was a lognormal function, in the range 3-14 nm. A time-dependent decrease of total reduced glutathione concentration by 36%, 50%, and 78% and an increase of NO level by 62%, 32%, respectively 24% compared to control were noticed. An up-regulation of NF-kB expression by 20%, 50% respectively 10% and of Nrf-2 by 139%, 58%, and 16% compared to control after 24, 48 and 72 hours was noticed also. The expression of IL-1β, IL-6, IL-8, and COX-2 was up-regulated in a time-dependent manner. Also, the expression of MMP-2 and MMP-9 were down-regulated after 48 and 72 hours, whereas their activities raised in a time-dependent manner. Exposure of cells to NPs up-regulated the expression of inducible NO synthase, as previously was shown, and probably this is the reason for the increased level of NO, that can react with the thiol groups of reduced glutathione molecules, diminishing its concentration Nrf2 is a transcription factor translocated in nucleus, under oxidative stress, where downstream gene expression activates in order to modulate the adaptive intracellular response against oxidative stress. The cross-talk between Nrf2 and NF-kB activities regulates the inflammatory processes. The activation of NF-kB could activate up-regulation of IL-1β, IL-6, and IL-8. The increase of COX-2 expression could be correlated with IL-1β one. Also, probably in response to the pro-inflammatory cytokines, MMP-2 and MMP-9 were induced and activated. In conclusion, the exposure of MRC-5 cells to SiO2-NPs generated inflammation in a time-dependent manner.

Keywords: inflammation, MRC-5 cells, oxidative stress, silica nanoparticles

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Authors: Angela O. Ugwu, Sunday Ocheni

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Background: Cancer-associated thrombosis (CAT) is a cause of morbidity and mortality among cancer patients. Several risk factors for developing venous thromboembolism (VTE) also coexist with cancer patients, such as chemotherapy and immobilization, thus contributing to the higher risk of VTE in cancer patients when compared to non-cancer patients. This study aimed to determine if there is any correlation between levels of some inflammatory cytokines/haematological parameters and Khorana scores of newly diagnosed chemotherapy naïve ambulatory cancer patients (CNACP). Methods: This was a cross-sectional analytical study carried out from June 2021 to May 2022. Eligible newly diagnosed cancer patients 18 years and above (case group) were enrolled consecutively from the adult Oncology Clinics of the University of Nigeria Teaching Hospital, Ituku/Ozalla (UNTH). The control group was blood donors at UNTH Ituku/Ozalla, Enugu blood bank, and healthy members of the Medical and Dental Consultants Association of Nigeria (MDCAN), UNTH Chapter. Blood samples collected from the participants were assayed for IL-6, TNF-Alpha, and haematological parameters such as haemoglobin, white blood cell count (WBC), and platelet count. Data were entered into an Excel worksheet and were then analyzed using Statistical Package for Social Sciences (SPSS) computer software version 21.0 for windows. A P value of < 0.05 was considered statistically significant. Results: A total of 200 participants (100 cases and 100 controls) were included in the study. The overall mean age of the participants was 47.42 ±15.1 (range 20-76). The sociodemographic characteristics of the two groups, including age, sex, educational level, body mass index (BMI), and occupation, were similar (P > 0.05). Following One Way ANOVA, there were significant differences between the mean levels of interleukin-6 (IL-6) (p = 0.036) and tumor necrotic factor-α (TNF-α) (p = 0.001) in the three Khorana score groups of the case group. Pearson’s correlation analysis showed a significant positive correlation between the Khorana scores and IL-6 (r=0.28, p = 0.031), TNF-α (r= 0.254, p= 0.011), and PLR (r= 0.240, p=0.016). The mean serum levels of IL-6 were significantly higher in CNACP than in the healthy controls [8.98 (8-12) pg/ml vs. 8.43 (2-10) pg/ml, P=0.0005]. There were also significant differences in the mean levels of the haemoglobin (Hb) level (P < 0.001)); white blood cell (WBC) count ((P < 0.001), and platelet (PL) count (P = 0.005) between the two groups of participants. Conclusion: There is a significant positive correlation between the serum levels of IL-6, TNF-α, and PLR and the Khorana scores of CNACP. The mean serum levels of IL-6, TNF-α, PLR, WBC, and PL count were significantly higher in CNACP than in the healthy controls. Ambulatory cancer patients with high-risk Khorana scores may benefit from anti-inflammatory drugs because of the positive correlation with inflammatory cytokines. Recommendations: Ambulatory cancer patients with 2 Khorana scores may benefit from thromboprophylaxis since they have higher Khorana scores. A multicenter study with a heterogeneous population and larger sample size is recommended in the future to further elucidate the relationship between IL-6, TNF-α, PLR, and the Khorana scores among cancer patients in the Nigerian population.

Keywords: thromboprophylaxis, cancer, Khorana scores, inflammatory cytokines, haematological parameters

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Authors: Kelly E. Tow, Peter Caputi, Claudia Rogge, Thomas Lee, Simon R. Knowles

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Inflammatory Bowel Disease (IBD) is a serious chronic health condition, characterised by inflammation of the gastrointestinal tract. Individuals with active IBD experience severe abdominal symptoms, which can adversely impact their physical and mental health, as well as their quality of life (QoL). Given that stress may exacerbate IBD symptoms and is frequently highlighted as a contributing factor for the development of psychological difficulties and poorer QoL, it is vital to investigate stress-management strategies aimed at improving the lives of those with IBD. The present study extends on the limited research in IBD cohorts by exploring the role of dispositional mindfulness and its impact on psychological well-being and QoL. The study examined how disease activity and dispositional mindfulness were related to psychological distress and QoL in a cohort of IBD patients. The potential role of dispositional mindfulness as a moderator between stress and anxiety, depression and QoL in these individuals was also examined. Participants included 47 patients with a clinical diagnosis of IBD. Each patient completed a series of psychological questionnaires and was assessed by a gastroenterologist to determine their disease activity levels. Correlation analyses indicated that disease activity was not significantly related to psychological distress or QoL in the sample of IBD patients. However, dispositional mindfulness was inversely related to psychological distress and positively related to QoL. Furthermore, moderation analyses demonstrated a significant interaction between stress and dispositional mindfulness on anxiety. These findings demonstrate that increased levels of dispositional mindfulness may be beneficial for individuals with IBD. Specifically, the results indicate positive links between dispositional mindfulness, general psychological well-being and QoL, and suggest that dispositional mindfulness may attenuate the negative impacts of stress on levels of anxiety in IBD patients. While further research is required to validate and expand on these findings, the current study highlights the importance of addressing psychological factors in IBD and indicates support for the use of mindfulness-based interventions for patients with the disease.

Keywords: anxiety, depression, dispositional mindfulness, inflammatory bowel disease, quality of life, stress

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Authors: Il-Ho Kim, Samuel Noh, Kwame McKenzie, Cyu-Chul Choi

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Introduction: The ‘stress of higher status’ hypothesis suggests that workers with higher-status occupations are more likely to experience work-to-family conflict (WFC) than those with lower-status occupations. Yet, the occupational difference in WFC and its mechanisms have not been explicitly explored within Asian culture. This present study examines (a) the association between occupational status and WFC and (b) the mediating roles of work-related stressors and resources, focused on gender perspectives using a sample of Korean immigrants. Methods: Data were derived from a cross-sectional survey of foreign born Korean immigrants who were currently working at least two years in the Greater Area of Toronto or surrounding towns. The sample was stratified for equivalent presentations of micro-business owners (N=555) and paid employees in diverse occupational categories (N=733). Results: We found gender differences and similarities in the link between occupational status and WFC and the mediating roles of work-related variables. Compared to skilled/unskilled counterparts, male immigrants in professional, service, and microbusiness jobs reported higher levels of WFC, whereas female immigrants in higher-status occupations were more likely to have WFC with the exception of the highest levels of WFC among microbusiness owners. Regardless of gender, both male and female immigrants who have longer weekly work hours, shift work schedule, and high emotional and psychological demands were significantly associated with high levels of WFC. However, skill development was related to WFC only among male immigrants. Regarding the mediating roles of work-related factors, among female immigrants, the occupational difference in WFC was fully mediated by weekly work hours, shift work schedule, and emotional and psychological demands with the exception of the case of microbusiness workers. Among male immigrants, the occupational differences remained virtually unchanged after controlling for these mediators. Conclusions: Our results partially confirmed the ‘stress of higher status’ hypothesis among female immigrants. Additionally, work-related stressors seem to be critical mediators of the link between occupations and WFC only for female immigrants.

Keywords: work-to-family conflict, gender, work conditions, job demands, job resources

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Authors: Basuki Supartono

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Introduction: Diabetic wound risks limb amputation, and the healing remains challenging. Chronic Hyperglycemia caused the insufficient inflammatory response and impaired ability of the cells to regenerate. Tissue Engineering Technique is mandatory. Methods: Tissue engineering (TE)-based therapy Utilizing mononuclear cells, plasma rich platelets, and collagen applied on the damaged tissue Results: TE technique resulting in acceptable outcomes. The wound healed completely in 2 months. No adverse effects. No allergic reaction. No morbidity and mortality Discussion: TE-based therapy utilizing mononuclear cells, plasma rich platelets, and collagen are safe and comfortable to fix damaged tissues. These components stop the chronic inflammatory process and increase cells' ability for regeneration and restoration of damaged tissues. Both of these allow the wound to regenerate and heal. Conclusion: TE-based therapy is safe and effectively treats unhealed diabetic lesion.

Keywords: diabetic foot lesion, tissue engineering technique, wound healing, stemcells

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Authors: Ritu Karwasra, Surender Singh

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Inflammation is an important physiological response of the body’s self-defense system that helps in eliminating and protecting organism from harmful stimuli and in tissue repair. It is a highly regulated protective response which helps in eliminating the initial cause of cell injury, and initiates the process of repair. The present study was designed to evaluate the ameliorative effect of pomegranate rind extract on pain and inflammation. Hydroalcoholic standardized rind extract of pomegranate at doses 50, 100 and 200 mg/kg and indomethacin (3 mg/kg) was tested against eddy’s hot plate induced thermal algesia, carrageenan (acute inflammation) and Complete Freund’s Adjuvant (chronic inflammation) induced models in Wistar rats. Parameters analyzed were inhibition of paw edema, measurement of joint diameter, levels of GSH, TBARS, SOD, TNF-α, radiographic imaging, tissue histology and synovial expression of pro-inflammatory cytokine receptor (TNF-R1). Radiological and light microscopical analysis were carried out to find out the bone damage in CFA-induced chronic inflammatory model. Findings of the present study revealed that pomegranate rind extract at a dose of 200 mg/kg caused a significant (p<0.05) reduction in paw swelling in both the inflammatory models. Nociceptive threshold was also significantly (p<0.05) improved. Immunohistochemical analysis of TNF-R1 in CFA-induced group showed elevated level, whereas reduction in level of TNF-R1 was observed in pomegranate (200 mg/kg). Henceforth, we might say that pomegranate produced a dose-dependent reduction in inflammation and pain along with the reduction in levels of oxidative stress markers and tissue histology, and the effect was found to be comparable to that of indomethacin. Thus, it can be concluded that pomegranate is a potential therapeutic target in the pathogenesis of inflammation and pain, and punicalagin is the major constituents found in rind extract might be responsible for the activity.

Keywords: carrageenan, inflammation, nociceptive-threshold, pomegranate, histopathology

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Authors: Yulistiani Yulistiani, Wenny Nilamsari, Laurin Winarso, Rizkiya Rizkiya, Zamrotul Izzah, Budi Suprapti, Arif Bachtiar

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Approximately, a million new cases of TB have been found out per year, making Indonesia as the second greatest country with TBC after India. Nevertheless, until now, there are still many patients failure to conventional therapy with oral anti tuberculosis. Thus, the discovery of supplement therapy is urgently needed. Many studies showed that probiotic had the positive impact in lung diseases, diarrhea, pneumonia and it was attributed to its capability to balance the level of cytokine pro-inflammatory and anti-inflammatory. It was demonstrated in active disease the production of IFN-γ is strongly depressed and IL-10 level increases. This study aimed to investigate the effect of probiotic (multi strains) and vitamin B complex supplementation on IFN-γ and IL-10 level in patients with TB infection during intensive phase therapy. A randomized controlled trial, open labeled was conducted in TB patients with the following criteria: 1) age 18-55 years old 2) receiving oral antituberculosis during intensive therapy 3) not using probiotic, vitamin B1, B6, B12 2 weeks before enrollment 4) willing to participate in this study and signed an informed consent. While, patients with HIV, pregnant, had the history of diabetes mellitus, using corticosteroid or other immunosuppressants were excluded. IFN-γ and IL-10 levels were drawn before observation and after a month observation. The assay was performed by ELISA. There were seven patients in treated group and five patients in controlled group obtained in this study. Between groups, there was no statistical difference in comorbid, age, and disease duration. The mean level of IFN-γ after a month observation increased in treated group and controlled group, which were 31.47 ± 105.46 pg/ml and 15.09 ± 24.23 pg/ml, respectively (p> 0.005). Although, there were not statistically different, treated group showed a greater increase of IFN-γ level than that of the controlled group. IFN-γ plays an important role in immune response to Mycobacterium Tuberculosis, by activating macrofag, monosit and furthermore killing Mycobacterium Tuberculosis. Thus the level was expected to increase after supplementation with probiotic and Vitamin B complex. While the mean level of IL-10 also increased after one month observation in the treated group and controlled group (4.28 ± 12.29 pg/ml and 5.77± 6.21 pg/ml, respectively) (p>0.005). To be compared, the increased level of IL-10 in the treated group were lower than the controlled group, although it was not statistically different. IL-10 is a cytokine anti-inflammatory, thus, the level after the observation was expected to decrease. In this study, a month therapy of probiotic and vitamin B complex was not able to demonstrate the decrease of the IL-10 level. It is suggested to prolong observation up to 2 months, because, in intensive phase, the level of cytokine anti-inflammatory is very high, so the longer therapy is needed. It is indicated that supplementation therapy with probiotic and vitamin B complex to Oral Anti-Tuberculosis may have a positive effect on increasing IFN-γ level and slowing the progression of IL-10.

Keywords: TB Infection, IFN-γ, IL-10, probiotic, vitamin B complex

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Authors: Mustafa Metin Donma, Orkide Donma

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Obesity in children particularly draws attention because it may threaten the individual’s future life due to many chronic diseases it may lead to. Most of these diseases, including obesity itself altogether are related to inflammation. For this reason, inflammation-related parameters gain importance. Within this context, complete blood cell counts, ratios or indices derived from these counts have recently found some platform to be used as inflammatory markers. So far, mostly adipokines were investigated within the field of obesity. The liver is at the center of the metabolic pathways network. Metabolic inflammation is closely associated with cellular dysfunction. In this study, hematologic inflammatory markers and two major hepatokines, cytokines produced predominantly by the liver, fibroblast growth factor-21 (FGF-21) and fetuin A were investigated in pediatric obesity. Two groups were constituted from seventy-six obese children based on World Health Organization criteria. Group 1 was composed of children whose age- and sex-adjusted body mass index (BMI) percentiles were between 95 and 99. Group 2 consists of children who are above the 99ᵗʰ percentile. The first and the latter groups were defined as obese (OB) and morbid obese (MO). Anthropometric measurements of the children were performed. Informed consent forms and the approval of the institutional ethics committee were obtained. Blood cell counts and ratios were determined by an automated hematology analyzer. The related ratios and indexes were calculated. Statistical evaluation of the data was performed by the SPSS program. There was no statistically significant difference in terms of neutrophil-to lymphocyte ratio, monocyte-to-high density lipoprotein cholesterol ratio and the platelet-to-lymphocyte ratio between the groups. Mean platelet volume and platelet distribution width values were decreased (p<0.05), total platelet count, red cell distribution width (RDW) and systemic immune inflammation index values were increased (p<0.01) in MO group. Both hepatokines were increased in the same group; however, increases were not statistically significant. In this group, also a strong correlation was calculated between FGF-21 and RDW when controlled by age, hematocrit, iron and ferritin (r=0.425; p<0.01). In conclusion, the association between RDW, a hematologic inflammatory marker, and FGF-21, an inflammation-related hepatokine, found in MO group is an important finding discriminating between OB and MO children. This association is even more powerful when controlled by age and iron-related parameters.

Keywords: childhood obesity, fetuin A , fibroblast growth factor-21, hematologic markers, red cell distribution width

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Authors: Daniel Osorio, Janneth Gonzalez, Andres Pinzon

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In this work, proteins and metabolic pathways associated with the neuroprotective response mediated by the synthetic neurosteroid tibolone under a palmitate-induced inflammatory model were identified by flux balance analysis (FBA). Three different metabolic scenarios (‘healthy’, ‘inflamed’ and ‘medicated’) were modeled over a gene expression data-driven constructed tissue-specific metabolic reconstruction of mature astrocytes. Astrocyte reconstruction was built, validated and constrained using three open source software packages (‘minval’, ‘g2f’ and ‘exp2flux’) released through the Comprehensive R Archive Network repositories during the development of this work. From our analysis, we predict that tibolone executes their neuroprotective effects through a reduction of neurotoxicity mediated by L-glutamate in astrocytes, inducing the activation several metabolic pathways with neuroprotective actions associated such as taurine metabolism, gluconeogenesis, calcium and the Peroxisome Proliferator Activated Receptor signaling pathways. Also, we found a tibolone associated increase in growth rate probably in concordance with previously reported side effects of steroid compounds in other human cell types.

Keywords: astrocytes, flux balance analysis, genome scale metabolic reconstruction, inflammation, neuroprotection, tibolone

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Authors: Marina G. Galitskaya, Svetlana G. Makarova, Andrey P. Fisenko.

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Children on medication-induced immunosuppression are at high risk of developing severe course infectious diseases. Therefore, preventive vaccination is especially important for these children. However, due to the immunosuppressive effects of treatment for the underlying disease, the effectiveness of vaccination may decrease below the protective level. In a multidisciplinary children's medical center, post-vaccination immunity was studied in 79 children aged 4-17 years. The children were divided into 2 groups: Group 1 (38 children) with kidney pathology (Nephrotic Syndrome) and Group 2 (41 children) with inflammatory bowel diseases (Ulcerative Colitis, Crohn's Disease). Both groups of children were vaccinated according to the national vaccination calendar and received immunosuppressive therapy (prednisolone, methotrexate, cyclosporine, and other drugs) for at least 1 year. Using the enzyme-linked immunosorbent assay method, specific IgG antibodies to vaccine-preventable infections were determined: measles, rubella, mumps, diphtheria, pertussis, tetanus, and hepatitis B. The study showed the percentage of children with positive IgG values for vaccine-preventable infections. The highest percentage of children had protective antibody levels to measles (84.2% in children with nephrotic syndrome and 92.6% in those with inflammatory bowel disease) and rubella (71% and 80.4%, respectively). The lowest percentage of children with protective antibodies was for hepatitis B (5.2% and 29.2% respectively). Antibodies to mumps, diphtheria, pertussis, and tetanus were found not in all children (from 39,4% to 82,9%). The remaining percentage of children did not have detectable IgG antibodies to vaccine-preventable infections. Not all children, despite the previous vaccination, preserved antibodies to vaccine-controlled infections and remained unprotected by specific IgG antibodies. The issue of a booster vaccine dose should be considered in children without contraindications to vaccination. Children receiving long-term immunosuppressive therapy require an individual vaccination approach, including a specific definition of the performed vaccination.

Keywords: immunosuppressive therapy, inflammatory bowel diseases, nephrotic syndrome, post-vaccination immunity, specific antibodies, vaccine-preventable infections.

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Authors: Yasmin Begum Mohammed

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Ketorolac tromethamine (KTM) is a non-steroidal anti-inflammatory drug with a potent analgesic and anti-inflammatory activity due to prostaglandin related inhibitory effect of drug. It is a non-selective cyclo-oxygenase inhibitor. The drug is currently used orally and intramuscularly in multiple divided doses, clinically for the management arthritis, cancer pain, post-surgical pain, and in the treatment of migraine pain. KTM has short biological half-life of 4 to 6 hours, which necessitates frequent dosing to retain the action. The frequent occurrence of gastrointestinal bleeding, perforation, peptic ulceration, and renal failure lead to the development of other drug delivery strategies for the appropriate delivery of KTM. The ideal solution would be to target the drug only to the cells or tissues affected by the disease. Drug targeting could be achieved effectively by liposomes that are biocompatible and biodegradable. The aim of the study was to develop a parenteral liposome formulation of KTM with improved efficacy while reducing side effects by targeting the inflammation due to arthritis. PEG-anchored (stealth) and non-PEG-anchored liposomes were prepared by thin film hydration technique followed by extrusion cycle and characterized for in vitro and in vivo. Stealth liposomes (SLs) exhibited increase in percent encapsulation efficiency (94%) and 52% percent of drug retention during release studies in 24 h with good stability for a period of 1 month at -20°C and 4°C. SLs showed about maximum 55% of edema inhibition with significant analgesic effect. SLs produced marked differences over those of non-SL formulations with an increase in area under plasma concentration time curve, t₁/₂, mean residence time, and reduced clearance. 0.3% of the drug was detected in arthritic induced paw with significantly reduced drug localization in liver, spleen, and kidney for SLs when compared to other conventional liposomes. Thus SLs help to increase the therapeutic efficacy of KTM by increasing the targeting potential at the inflammatory region.

Keywords: biodistribution, ketorolac tromethamine, stealth liposomes, thin film hydration technique

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Authors: K. Azadeh, M. Ghasemi, S. Fazelifar

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Aim: Changes in stress hormones can be modify response of immune system. Cortisol as the most important body corticosteroid is anti-inflammatory and immunosuppressive hormone. Normal levels of cortisol in humans has fluctuated during the day, In other words, cortisol is released periodically, and regulate through the release of ACTH circadian rhythm in every day. Therefore, the aim of this study was to determine the effects of Chamomile on serum levels of inflammatory indexes to a bout of eccentric exercise in young women. Methodology: 32 women were randomly divided into 4 groups: high dose of Chamomile, low dose of Chamomile, ibuprofen and placebo group. Eccentric exercise included 5 set and rest period between sets was 1 minute. For this purpose, subjects warm up 10 min and then done eccentric exercise. Each participant completed 15 repetitions with optional 20 kg weight or until can’t continue moving. When the subject was no longer able to continue to move, immediately decreased 5 kg from the weight and the protocol continued until cause exhaustion or complete 15 repetitions. Also, subjects received specified amount of ibuprofen and Chamomile capsules in target groups. Blood samples in 6 stages (pre of starting pill, pre of exercise protocol, 4, 24, 48 and 72 hours after eccentric exercise) was obtained. The levels of cortisol and adrenocorticotropic hormone levels were measured by ELISA way. K-S test to determine the normality of the data and analysis of variance for repeated measures was used to analyze the data. A significant difference in the p < 0/05 accepted. Results: The results showed that Individual characteristics including height, weight, age and body mass index were not significantly different among the four groups. Analyze of data showed that cortisol and ACTH basic levels significantly decreased after supplementation consumption, but then gradually significantly increased in all stages of post exercise. In High dose of Chamomile group, increasing tendency of post exercise somewhat less than other groups, but not to a significant level. The inter-group analysis results indicate that time effect had a significant impact in different stages of the groups. Conclusion: The results of this study, one session of eccentric exercise increased cortisol and ACTH hormone. The results represent the effect of high dose of Chamomile in the prevention and reduction of increased stress hormone levels. As regards use of medicinal plants and ibuprofen as a pain medication and inflammation has spread among athletes and non-athletes, the results of this research can provide information about the advantages and disadvantages of using medicinal plants and ibuprofen.

Keywords: chamomile, inflammatory indexes, eccentric exercise, young girls

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Authors: Margarita Ivanova, Julia Dao, Andrew Friedman, Neil Kasaci, Rekha Gopal, Ozlem Goker-Alpan

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In Fabry disease (FD), α-galactosidase A (α-Gal A) deficiency leads to the accumulation of globotriaosylceramide (Lyso-Gb3 and Gb3), triggering a pathologic cascade that causes the severity of organs damage. The heart is one of the several organs with high sensitivity to the α-Gal A deficiency. A subgroup of patients with significant residual of α-Gal A activity with primary cardiac involvement is occasionally referred to as “cardiac variant.” The cardiovascular complications are most frequently encountered, contributing substantially to morbidity, and are the leading cause of premature death in male and female patients with FD. The deposition of Lyso-Gb-3 and Gb-3 within the myocardium affects cardiac function with resultant progressive cardiovascular pathology. Gb-3 and Lyso-Gb-3 accumulation at the cellular level trigger a cascade of events leading to end-stage fibrosis. In the cardiac tissue, Lyso-Gb-3 deposition is associated with the increased release of inflammatory factors and transforming growth factors. Infiltration of lymphocytes and macrophages into endomyocardial tissue indicates that inflammation plays a significant role in cardiac damage. Moreover, accumulated data suggest that chronic inflammation leads to multisystemic FD pathology even under enzyme replacement therapy (ERT). NF-κB activation plays a subsequent role in the inflammatory response to cardiac dysfunction and advanced heart failure in the general population. TNFalpha/NF-κB signaling protects the myocardial evoking by ischemic preconditioning; however, this protective effect depends on the concentration of TNF-α. Thus, we hypothesize that TNF-α is a critical factor in determining the grade of cardio-pathology. Cardiac hypertrophy corresponds to the expansion of the coronary vasculature to maintain a sufficient supply of nutrients and oxygen. Coronary activation of angiogenesis and fibrosis plays a vital role in cardiac vascularization, hypertrophy, and tissue remodeling. We suggest that the interaction between the inflammatory pathways and cardiac vascularization is a bi-directional process controlled by secreted cytokines and growth factors. The co-coordination of these two processes has never been explored in FD. In a cohort of 40 patients with FD, biomarkers associated with inflammation and cardio hypertrophic remodeling were studied. FD patients were categorized into three groups based on LVmass/DSA, LVEF, and ECG abnormalities: FD with no cardio complication, FD with moderate cardio complication, and severe cardio complication. Serum levels of NF-kB, TNFalpha, Il-6, Il-2, MCP1, ING-gamma, VEGF, IGF-1, TGFβ, and FGF2 were quantified by enzyme-linked immunosorbent assays (ELISA). Among the biomarkers, MCP-1, INF-gamma, VEGF, TNF-alpha, and TGF-beta were elevated in FD patients. Some of these biomarkers also have the potential to correlate with cardio pathology in FD. Conclusion: The study provides information about the role of inflammatory pathways and biomarkers of cardio hypertrophic remodeling in FD patients. This study will also reveal the mechanisms that link intracellular accumulation of Lyso-GB-3 and Gb3 to the development of cardiomyopathy with myocardial thickening and resultant fibrosis.

Keywords: biomarkers, Fabry disease, inflammation, growth factors

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Authors: Eman Abdullah Morsi, Hend Okasha, Heba Abdel Hady, Mortada El-Sayed, Mohamed Abbas Shemis

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Context: Linum usitatissimum (Linn), known as Flaxseed, is one of the most important medicinal plants traditionally used for various health as nutritional purposes. Objective: Estimation of total phenolic and flavonoid contents as well as evaluate the antioxidant using α, α-diphenyl-β-picrylhydrazyl (DPPH), 2-2'azinobis (3-ethylbenzthiazoline-6-sulphonic acid (ABTS) and total antioxidant capacity (TAC) assay and investigation of anti-inflammatory by Bovine serum albumin (BSA) and anticancer activities of hepatocellular carcinoma cell line (HepG2) and breast cancer cell line (MCF7) have been applied on hexane, ethyl acetate, n-butanol and methanol extracts and also, fractions of methonal extract (hexane, ethyl acetate and n-butanol). Materials and Methods: Phenolic and flavonoid contents were detected using spectrophotometric and colorimetric assays. Antioxidant and anti-inflammatory activities were estimated in-vitro. Anticancer activity of extracts and fractions of methanolic extract were tested on (HepG2) and (MCF7). Results: Methanolic extract and its ethyl acetate fraction contain higher contents of total phenols and flavonoids. In addition, methanolic extract had higher antioxidant activity. Butanolic and ethyl acetate fractions yielded higher percent of inhibition of protein denaturation. Meanwhile, ethyl acetate fraction and methanolic extract had anticancer activity against HepG2 and MCF7 (IC50=60 ± 0.24 and 29.4 ± 0.12µg.mL⁻¹) and (IC50=94.7 ± 0.21 and 227 ± 0.48µg.mL⁻¹), respectively. In Gas chromatography-mass spectrometry (GC-MS) analysis, methanolic extract has 32 compounds, whereas; ethyl acetate and butanol fractions contain 40 and 36 compounds, respectively. Conclusion: Flaxseed contains totally different biologically active compounds that have been found to possess good variable activities, which can protect human body against several diseases.

Keywords: phenolic content, flavonoid content, HepG2, MCF7, hemolysis-assay, flaxseed

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Authors: Vishvas N. Patel, Mehul Chorawala

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Currently, according to the authors best knowledge there are less effective therapeutic agents to limit intestinal mucosa damage associated with inflammatory bowel disease (IBD). Clinical studies have shown beneficial effects of several probiotics in patients of IBD. Probiotics are live organisms; confer a health benefit to the host by modulating immunoinflammation and oxidative stress. Although probiotics in murine and human improve disease severity, very little is known about the specific contribution of cell wall contents of probiotics in IBD. Herein, we investigated the ameliorative potential of cell wall contents of Lactobacillus casei (LC) in lipopolysaccharide (LPS)-induced murine colitis. Methods: Colitis was induced in LPS-sensitized rats by intracolonic instillation of LPS (50 µg/rat) for consecutive 14 days. Concurrently, cell wall contents isolated from 103, 106 and 109 CFU of LC was given subcutaneously to each rat for 21 days, considering sulfasalazine (100 mg/kg, p.o.) as standard. The severity of colitis was assessed by body weight loss, food intake, stool consistency, rectal bleeding, colon weight/length, spleen weight and histological analysis. Colonic inflammatory markers (myeloperoxidase (MPO) activity, C-reactive protein and proinflammatory cytokines) and oxidative stress markers (malondialdehyde, reduced glutathione and nitric oxide) were also assayed. Results: Cell wall contents of isolated from 106 and 109 CFU of LC significantly improved the severity of colitis by reducing body weight loss and diarrhea & bleeding incidence, improving food intake, colon weight/length, spleen weight and microscopic damage to the colonic mucosa. The treatment also reduced levels of inflammatory and oxidative stress markers and boosted antioxidant molecule. However, cell wall contents of isolated from 103 were ineffective. Conclusion: In conclusion, cell wall contents of LC attenuate LPS-induced colitis by modulating immuno-inflammation and oxidative stress.

Keywords: probiotics, Lactobacillus casei, immuno-inflammation, oxidative stress, lipopolysaccharide, colitis

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Authors: Grace McCambridge, Alanna Keady, Madhur Agrawal, Dequina Nicholas Alvarado, Barbara Nikolajczyk, Leena Panneerseelan-Bharath

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Age is a non-modifiable risk factor for the inflammation that underlies pathologies such as type 2 diabetes mellitus (T2DM). Inflammation, as indicated by circulating cytokines, rises in aging, but mechanisms that promote this ‘inflammaging’ remain poorly defined. Furthermore, downstream consequences of inflammaging, including the development of an inflammatory profile that predicts comorbidities like T2DM, remain speculative. We tested the possibility that natural aging-associated changes in autophagy, a process that is compromised in both aging and T2DM, regulates inflammatory profiles in older subjects. Our data showed that circulating CD4⁺ T cells from older compared to younger subjects have (i) defects in autophagy; (ii) higher mitochondria accumulation; (iii) a failure to metabolically shift from oxidative phosphorylation to anaerobic glycolysis upon αCD3/CD28 activation; (iv) more reactive oxygen species (ROS) accumulation; and (v) a cytokine profile that recapitulates the Th17 profile that predicts T2DM. ROS scavenging in cells from older subjects restored mitochondrial mass and membrane potential (indicators of improved autophagy) and reduced Th17 cytokines to amounts made by T cells from younger subjects. Knock-down of the autophagy protein Atg3 in T cells from younger subjects increased mitochondrial accumulation and Th17 cytokines. To begin translating these findings to clinical practice, we showed that physiological concentrations of the diabetes drug metformin (100 µM) added in vitro enhanced autophagy, prevented mitochondria and ROS accumulation, increased anaerobic glycolysis, and decreased Th17 cytokines in activated CD4⁺ T cells from older subjects. Metformin therefore improves autophagy and multiple downstream pro-inflammatory mechanisms CD4⁺ T cells from older subjects. We conclude that autophagy improvement ameliorates the development of a T2DM-predictive Th17 profile in aging, and thus holds promise for delay or prevention of aging-associated metabolic decline.

Keywords: autophagy, mitochondrial turnover, ROS, glycolysis

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Authors: Leyla Sattarzadeh, Maghsoud Peeri, Mohammadali Azarbaijani, Hasan Matin Homaee

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Inflammation by various mechanisms may cause atherosclerosis. Systemic circulating inflammatory markers such as C-reactive protein (CRP), pro-inflammatory cytokines such as Interleukin-6 (IL-6) and adhesion molecules like Intracellular Adhesion Molecule-1 (ICAM-1) are the predictors of cardiovascular diseases. Regarding the conflicting results about the effect of resistance exercise training on these inflammatory markers, the present study aimed to examine the effect of eight week different patterns of resistance exercise training on CRP, IL-6 and ICAM-1 levels in healthy untrained women. 40 volunteered and healthy untrained female university students (aged: 21+ 3 yr., Body Mass Index: 21.5+ 3.5 kg/m2) were selected purposefully and divided into three groups. At the end of training protocol and after subjects drop during the protocol in upper body exercise training (n=11), lower body (n=12) completed the eight week of training period although the control group (n=7) did anything. Blood samples gathered pre and post experimental period and CRP, IL-6 and ICAM-1 levels were evaluated using special laboratory kits, then the difference of pre and post values of each indices analyzed using one way Analysis of Variance (α < 0.05). The results of one way ANOVA for difference of pre and post values of CRP and ICAM-1 showed no significant changes due to the exercise training. But there were significant differences between groups about IL-6. Tukey post- hoc test indicated that there is significant difference between the differences of pre and post values of IL-6 between lower body exercise training group and control group, and eight weeks of lower body exercise training lead to significant changes in IL-6 values. There were no changes in anthropometric indices. The findings show that the different patterns of upper and lower body exercise training by involving the different amount of muscles altered the IL-6 values in lower body exercise training group probably because of engaging the bigger amount of muscles, but showed any significant changes about CRP and ICAM-1 probably due to intensity and duration of exercise or the lower levels of these markers at baseline of healthy people.

Keywords: C-reactive protein, interleukin-6, intracellular adhesion molecule-1, resistance training

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Authors: Mukesh Saran, Ashima Bagaria

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Green nanotechnology is the most researched field in the current scenario. Herein we study the synthesis of Zinc and Ferrous nanoparticles using Moringa oleifera leaf extracts. Our protocol using established protocols heat treatment of plant extracts along with the solution of copper sulphate in the ratio of 1:1. The leaf extracts of Moringa oleifera were prepared in deionized water. Copper sulfate solution (1mM) was added to this, and the change in color of the solution was observed indicating the formation of Cu nanoparticles. The as biosynthesized Cu nanoparticles were characterized with the help of Scanning Electron Microscopy (SEM), and Fourier Transforms Infrared Spectroscopy (FTIR). It was observed that the leaf extracts of Moringa oleifera can reduce copper ions into copper nanoparticles within 8 to 10 min of reaction time. The method thus can be used for rapid and eco-friendly biosynthesis of stable copper nanoparticles. Further, we checked their antimicrobial and antioxidant potential, and it was observed that maximum antioxidant activity was observed for the particles prepared using the heating method. The maximum antibacterial activity was observed in Streptomyces grisveus particles and in Triochoderma Reesei for the maximum antifungal activity. At present, we are engaged in studying the anti-inflammatory activities of these as prepared nanoparticles.

Keywords: green synthesis, antibacterial, antioxidant, antifungal, anti-inflammatory

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Authors: Dzatur Rizqi Fathienah Syarifuddin, Isharyah Sunarno, Eddy Hartono, Siti Maisuri T. Chalid

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Introduction: The potential impact of coronavirus disease 2019 (COVID-19) on the health of expectant mothers and fetuses has strained attention. Pregnant women are considered a vulnerable category to respiratory infections. Moreover, several inflammatory cytokines are 2-100 times more abundant in COVID-19 with cytokine storms than in normal individuals; interleukin 6 (IL-6) exhibits much higher elevations. Investigating potential relationships between IL-6 serum levels and the severity of COVID-19 symptoms in pregnant women is the aim of this study. Material and Methods: Sixty-two eligible pregnant women were divided into a positive COVID-19 group (n=31) and a negative COVID-19 group (n=31) in this cross-sectional study. The research subjects were selected using consecutive sampling. The IL-6 was measured from a vein blood specimen using ELISA methods. Results: The COVID-19 positive group had a higher median IL-6 serum level (45.35 (35.15- 153.99) vs. 38.86 ± 11.43 (15.02-59.52), p=0.03) than the negative group. On the other hand, the IL-6 serum level had comparable value according to the COVID-19 symptoms severity (88.35 ± 36.14 ng/mL vs. 51.09 ± 25.48 ng/mL vs. 56.02 ± 33.20 ng/mL in moderate symptoms, mild symptoms, and asymptomatic, respectively; p=0.152). Conclusion: Although the IL-6 serum levels are not related to COVID-19 symptoms severity, an elevated of this biomarker was found in pregnant women with affected diagnoses.

Keywords: interleukin-6, pregnancy, COVID-19, several inflammatory

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Authors: Islam Nowisser, Noha Farag, Mohamed El Azizi

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Helicobacter pylori is a highly important human pathogen which inhabits about 50% of the population worldwide. Infection with this bacteria is very hard to treat, with high probability of recurrence. H. pylori causes severe gastric diseases, including peptic ulcer, gastritis, and gastric cancer, which has been linked to chronic inflammation. The infection has been reported to be associated with high levels of pro-inflammatory cytokines, especially IL-1β and TNF-α. The aim of the current study is to investigate the molecular mechanisms by which H. pylori activates NLRP3 inflammasome and its contribution to Il-1 β production in an innate cellular model. H. pylori PMSS1 and G27 standard strains, as well as the PMSS1 isogenic mutant strain PMSS1ΔVacA and G27ΔVacA, G27ΔCagA in addition to clinical isolates obtained from biopsy samples from the antrum and corpus mucosa of chronic gastritis patients, were used to establish infection in RAW-264.7 macrophages. The production levels of TNF-α and IL-1β was assessed using ELISA. Since expression of these cytokines is often regulated by the transcription factor complex, nuclear factor-kB (NF-kB), the activation of NF-κB in H. pylori infected cells was also evaluated by luciferase assay. Genomic DNA was extracted from bacterial cultures of H. pylori clinical isolates as well as the standard strains and their corresponding mutants, where they were evaluated for the cagA pathogenicity island and vacA expression. The correlation between these findings and expression of the cagA Pathogenicity Island and vacA in the bacteria was also investigated. The results showed IL-1β, and TNF-α production significantly increased in raw macrophages following H. pylori infection. The cagA+ and vacA+ H. pylori strains induced significant production of IL-1β compared to cagA- and vacA- strains. The activation pattern of NF-κB was correlated in the isolates to their cagA and vacA expression profiles. A similar finding could not be confirmed for TNF-α production. Our study shows the ability of H. pylori to activate NF-kB and induce significant IL-1β production as a possible mechanism for the augmented inflammatory response seen in subjects infected with cagA+ and vacA+ H. pylori strains that would lead to the progression to more severe form of the disease.

Keywords: Helicobacter pylori, IL-1β, inflammatory cytokines, nuclear factor KB, TNF-α

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Authors: R. N. Nataria, A. D. Paryuni, R. Wasito

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Layer farms in Indonesia have still obstacles to increasing their productivity, especially due to poultry diseases. The red onion (Allium ascalonicum L.) is a plant that contains flavonoid and saponin. Flavonoid is useful as anti-inflammatory and antioxidant while saponin is useful as antivirus, anti-inflammatory, antifungal, and immunomodulator. This study aimed to know and determine the effect of onion extracts to pulmonary histopathological lesions in layer chickens which raised in the battery cage. This study used eighteen layer chickens at seventeen days old. The eighteen layer chickens were divided into three groups of six each, namely without administration of red onion extract (Group I), with administration red onion extract through drinking water (Group II) and with administration red onion extract peroral (Group III). Every ten days, six chickens were necropsied and then the lungs were processed for histopathological preparations and stained with routine hematoxylin and eosin. The results showed that the lungs of the Group I had severe congestion and diffuse hemorrhages. In Group II, lungs had moderate congestion and hemorrhages. In group III, lungs had mild congestion and hemorrhages. It is concluded, that red onion extract apparently has reduced the lungs lesions in layer chickens.

Keywords: histopathological lesions, layers, lungs, poultry diseases, red onion extract

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Authors: Karissa A. Graham

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Pyoderma gangrenosum (PG) is a prototypic autoinflammatory neutrophilic dermatosis that is a rare disorder. It presents a diagnostic challenge owing to its variable presentation, clinical overlap with other conditions, it is often associated with other systemic conditions, and there is no definitive histological or laboratory characteristic. The Delphai consensus for PG includes the presence of at least one ulcer on the anterior lower limb. Systemic corticosteroids and immunosuppressive therapies are the mainstay treatment for PG. We describe a case report of delayed diagnosis of ulcerative pyoderma gangrenosum in a 44-year-old male on his forearm. The patient presented with an infected ulcer on his right forearm that had been present for over three years. The patient was a Type 2 Diabetic with no personal or family history of inflammatory bowel disease or other autoimmune diseases. The patient was initially investigated for malignancy, but biopsies returned as chronic inflammatory tissue with neutrophilic infiltrate and no malignancy. The patient was commenced on systemic prednisone for the treatment of pyoderma gangrenosum. The diagnosis of ulcerative PG poses a challenge given the vast differential diagnosis for a cutaneous ulcer (i.e., malignant, vascular, autoimmune, trauma, infective, etc.). Diagnostic accuracy is important given that the treatment for PG with steroids does not go without risks and indeed may be contraindicated in other potential causes of the ulcer. Indeed, more common and more sinister causes of ulcers should be investigated first, as death from PG is quite rare.

Keywords: dermatological diagnosis, dermatosis, pyoderma gangrenosum, rare presentation

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Authors: Sina Mahdavi

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Background and Objective: Multiple sclerosis (MS) is the most common inflammatory autoimmune disease of the central nervous system (CNS) that affects the myelination process in the CNS. Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially the John Cunningham virus (JCV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on JCV infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis", " John Cunningham virus ", and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2019 and 2022 were searched, and 12 articles were chosen, studied, and analyzed. Results: MS patients are candidates for natalizumab therapy, which inhibits lymphocyte migration and increases the risk of progressive multifocal leukoencephalopathy (PML), a rare lytic infection of glial cells caused by JCV. Oligodendrocytes may be the target of JCV infection in the central nervous system (CNS). Conclusion: There is a high expression of JCV during the natalizumab treatment period for MS patients, suggesting that the virus may play a role in the development of MS by inducing an inflammatory state. Therefore, it is necessary to evaluate anti-JCV antibody serum as an important risk factor for the development of PML before deciding on the treatment course for these patients.

Keywords: multiple sclerosis, John Cunningham virus, central nervous system, autoimmunity

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Authors: Mansi Srivastava, Uzma Saqib, Adnan Naim, Anjali Roy, Dongfang Liu, Deepak Bhatnagar, Ravinder Ravinder, Mirza S. Baig

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Macrophages polarize to proinflammatory M1 or anti-inflammatory M2 states with distinct physiological functions. This transition within the M1 to M2 phenotypes decides the nature, duration, and severity of an inflammatory response. However, inspite of a substantial understanding of the fate of these phenotypes, the underlying molecular mechanisms are not well understood. We have investigated the role of Neuronal nitric oxide synthase (NOS1) mediated regulation of Activator protein 1 (AP-1) transcription factor in macrophages as a critical effector of macrophage phenotypic change. Activator protein 1 (AP-1) is a group of dimeric transcription factors composed of jun, Fos, and ATF family proteins. We determined that NOS1-derived nitric oxide (NO) facilitate Fos and jun interaction which induces IL12 & IL23 expression. Pharmacological inhibition of NOS1 inhibits Fos and jun interaction but increases ATF2 and Fos dimerization. Switching of Fos and jun dimer to ATF2 and jun dimerization switches phenotype from IL–12high IL-23high IL-10low to IL–12low IL-23lowIL-10high phenotype, respectively. Together, these findings highlight a key role of the TLR4-NOS1-AP1 signaling axis in regulating macrophage polarization.

Keywords: inflammation, macrophage, lipopolysaccharide (LPS), proinflammatory cytokines, activator protein 1 (AP-1), neuronal nitric oxide synthase (NOS1)

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Authors: Uzma Saqib, Mirza S. Baig

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Myeloid differentiation primary response protein 88 (MYD88) has long been considered a central player in the inflammatory pathway. Recent studies clearly suggest that it is an important therapeutic target in inflammation. On the other hand, a recent study on the interaction between the orphan nuclear receptor (Nur77) and p38α, leading to increased lipopolysaccharide-induced hyperinflammatory response, suggests this binary complex as a therapeutic target. In this study, we have designed inhibitors that can inhibit both MYD88 and Nur77 at the same time. Since both MYD88 and Nur77 are an integral part of the pathways involving lipopolysaccharide-induced activation of NF-κB-mediated inflammation, we tried to target both proteins with the same library in order to retrieve compounds having dual inhibitory properties. To perform this, we developed a homodimeric model of MYD88 and, along with the crystal structure of Nur77, screened a virtual library of compounds from the traditional Chinese medicine database containing ~61,000 compounds. We analyzed the resulting hits for their efficacy for dual binding and probed them for developing a common pharmacophore model that could be used as a prototype to screen compound libraries as well as to guide combinatorial library design to search for ideal dual-target inhibitors. Thus, our study explores the identification of novel leads having dual inhibiting effects due to binding to both MYD88 and Nur77 targets.

Keywords: drug design, Nur77, MYD88, inflammation

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Authors: Eryati Darwin, Eka Fithra Elfi, Indria Hafizah

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Background: Physical exercise induces a pattern of hormonal and immunological responses that prevent endothelial dysfunction by maintaining the availability of nitric oxide (NO). Regular and moderate exercise stimulates NO release, that can be considered as protective factor of cardiovascular diseases, while strenuous exercise induces increased levels in a number of pro-inflammatory and anti-inflammatory cytokines. Pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) triggers endothelial activation which results in an increased vascular permeability. Nuclear gene factor kappa B (NF-κB) activates biological effect of TNF-α. Aim of Study: To determine the effect of physical exercise on the endothelial and skeletal muscle, we measured the level of NF-κB on rats’ serum, macrophages, and myocytes after strenuous physical exercise. Methods: 30 male Rattus norvegicus in the age of eight weeks were randomly divided into five groups (each containing six), and there were treated groups (T) and control group (C). The treated groups obtain strenuous physical exercise by ran on treadmill at 32 m/minutes for 1 hour or until exhaustion. Blood samples, myocytes of gastrocnemius muscle, and intraperitoneal macrophages were collected sequentially. There were investigated immediately, 2 hours, 6 hours, and 24 hours (T1, T2, T3, and T4) after sacrifice. The levels of NF-κB were measured by ELISA methods. Results: From our study, we found that the levels of NF-κB on myocytes in treated group from which its specimen was taken immediately (T1), 2 hours after treadmill (T2), and 6 hours after treadmill (T3) were significantly higher than control group (p<0.05), while the group from which its specimen was taken 24 hours after treadmill, was no significantly different (p>0.05). Also on macrophages, NF-κB in treated groups T1, T2, and T3 was significantly higher than control group (p<0.05), but there was no difference between T4 and control group (p>0.05). The level of serum NF-κB was not significantly different between treatment group as well as compared to control group (p>0.05). Serum NF-κB was significantly higher than the level on macrophages and myocytes (p<0.05). Conclusion: This study demonstrated that strenuous physical exercise stimulates the activation of NF-κB that plays a role in vascular inflammation and muscular damage, and may be recovered after resting period.

Keywords: endothelial function, inflammation, NFkB, physical exercise

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Authors: Dionne Coley B. A.

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The role of a lawyer as a mediator is to be impartial in assisting parties to arrive at a decision. This decision should be made in a voluntary and mutually acceptable manner where the mediator encourages the parties to communicate, identify their interests, assess risks and consider settlement options. One of the key components to mediation is impartiality where mediators are to have a duty to remain impartial throughout the course of mediation and uphold an “objective” demeanor with both parties. The question is whether a mediator should take on evaluative role while encouraging the parties to come to a decision. This means that the mediator would not only encourage dialogue and responses between the parties but also assess and provide an opinion on the matter. This paper submits the argument that the role of a mediator should not be one of evaluation as this does not encourage the dialogue, process or desired outcomes associated with mediation.

Keywords: evaluation, lawyer, mediation, reform

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Authors: Yulistiani Yulistiani, Zamrotul Izzah, Lintang Bismantara, Wenny Putri Nilamsari, Arif Bachtiar, Budi Suprapti

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Interferon-gamma (IFN-γ) and interleukin-6 (IL-6) are pro-inflammatory cytokines, which have the protective immune response against Tuberculosis (TB). Indeed, pro-inflammatory cytokines Mycobacterium tuberculosis antigen-specific CD4+ and CD8+ T cells and NK cells increase the level of production of IFN-γ, a cytokine critical for augmenting the microbicidal activity of phagocytes. On the other hand, M. tuberculosis reduces the effects of IFN-γ by inhibiting the transcription of IFN-γ- responsive genes and by inducing the secretion of IL-6, which inhibits IFN-γ signaling. Probiotics Lactobacillus sp. and Bifidobacterium sp. were known to increase IFN-γ production in vivo, while vitamin B1, B6, and B12 worked on macrophages and releasing cytokines. Therefore, the present study was to evaluate the effect of probiotics and vitamin B supplement on changes of plasma cytokine levels in active pulmonary TB. From October to November 2016, twelve M. tuberculosis-infected patients starting anti-TB drugs were recruited, then divided into two groups. Seven patients were given a combination of probiotics and vitamin B, while five patients were in the control group. Plasma IFN-γ and IL-6 levels were measured by the ELISA kit before and a month after treatment. IFN-γ levels raised in four patients receiving the supplement (P = 0.743), while IL-6 increased in three patients in this group until day 30 of treatment (P = 0.298). Taken together, these results show the promising effect of probiotics and vitamin B on stimulation of IFN-γ and IL-6 production during intensive therapy of TB.

Keywords: interferon-gamma, interleukin-6, probiotic, tuberculosis

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Authors: Rachid Kacem

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Excessive recruitment of Neutrophils into the lungs is a hallmark of several chronic inflammatory disorders such as emphysema and COPD. The resulting of this recruitment is the pathogenesis of lungs which is characterized by an imbalance between leukocyte serine proteinases mainly neutrophil elastase and the physiological inhibitors. The development of emphysema and remodeling of airway tissue occurred when neutrophil migrate into the lungs with more release of elastase and other proteolytic enzymes. Many reports have demonstrated that the extracts from medicinal plants such as Nigella sativa (L.) seeds extracts have anti-elastase activity; this is mainly due to the enrichment of the extracts with many bioactive molecules mainly phenolic compounds. Neutrophil serine proteases including human neutrophil elastase are involved in many inflammatory diseases, such as chronic obstructive pulmonary disease and emphysema. Since the current therapies for these diseases are inadequate and have numerous adverse effects, there is an acute need of potential alternative therapies. The natural protease inhibitors have received increasing attention as useful tools for potential utilization in pharmacology. This work is elucidating the most important natural phenolic substances that have been reported recently for their effectiveness as natural anti-elastase molecules, and hence, to the possibility of their use in the field of pharmaceuticals.

Keywords: medicinal plants, phenols, elastase, anti-elastase, chronic obstructive pulmonary disease, COPD, emphysema

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Authors: Amruta D. S. Pathare, Indira Hinduja, Kusum Zaveri

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Implantation failure (IF) even after the good-quality embryo transfer (ET) in the physiologically normal endometrium is the main obstacle in in vitro fertilization (IVF). Various microarray studies have been performed worldwide to elucidate the genes requisite for endometrial receptivity. These studies have included the population based on different phases of menstrual cycle during natural cycle and stimulated cycle in normal fertile women. Additionally, the literature is also available in recurrent implantation failure patients versus oocyte donors in natural cycle. However, for the first time, we aim to study the genomics of endometrial receptivity in IF patients under controlled ovarian stimulation (COS) during which ET is generally practised in IVF. Endometrial gene expression profiling in IF patients (n=10) and oocyte donors (n=8) were compared during window of implantation under COS by whole genome microarray (using Illumina platform). Enrichment analysis of microarray data was performed to determine dys-regulated biological functions and pathways using Database for Annotation, Visualization and Integrated Discovery, v6.8 (DAVID). The enrichment mapping was performed with the help of Cytoscape software. Microarray results were validated by real-time PCR. Localization of genes related to immune response (Progestagen-Associated Endometrial Protein (PAEP), Leukaemia Inhibitory Factor (LIF), Interleukin-6 Signal Transducer (IL6ST) was detected by immunohistochemistry. The study revealed 418 genes downregulated and 519 genes upregulated in IF patients compared to healthy fertile controls. The gene ontology, pathway analysis and enrichment mapping revealed significant downregulation in activation and regulation of immune and inflammation response in IF patients under COS. The lower expression of Progestagen Associated Endometrial Protein (PAEP), Leukemia Inhibitory Factor (LIF) and Interleukin 6 Signal Transducer (IL6ST) in cases compared to controls by real time and immunohistochemistry suggests the functional importance of these genes. The study was proved useful to uncover the probable reason of implantation failure being imbalance of immune and inflammatory regulation in our group of subjects. Based on the present study findings, a panel of significant dysregulated genes related to immune and inflammatory pathways needs to be further substantiated in larger cohort in natural as well as stimulated cycle. Upon which these genes could be screened in IF patients during window of implantation (WOI) before going for embryo transfer or any other immunological treatment. This would help to estimate the regulation of specific immune response during WOI in a patient. The appropriate treatment of either activation of immune response or suppression of immune response can be then attempted in IF patients to enhance the receptivity of endometrium.

Keywords: endometrial receptivity, immune and inflammatory response, gene expression microarray, window of implantation

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