Search results for: inflammatory indexes
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1144

Search results for: inflammatory indexes

904 Silica Nanoparticles Induced Oxidative Stress and Inflammation in MRC-5 Human Lung Fibroblasts

Authors: Anca Dinischiotu, Sorina Nicoleta Voicu

Abstract:

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

Procedia PDF Downloads 112
903 Correlation between the Levels of Some Inflammatory Cytokines/Haematological Parameters and Khorana Scores of Newly Diagnosed Ambulatory Cancer Patients

Authors: Angela O. Ugwu, Sunday Ocheni

Abstract:

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

Procedia PDF Downloads 52
902 Psychological Distress and Quality of Life in Inflammatory Bowel Disease Patients: The Role of Dispositional Mindfulness

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

Abstract:

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

Procedia PDF Downloads 134
901 Treatment of Interferograms Image of Perturbation Processes in Metallic Samples by Optical Method

Authors: Daira Radouane, Naim Boudmagh, Hamada Adel

Abstract:

The but of this handling is to use the technique of the shearing with a mechanism lapping machine of image: a prism of Wollaston. We want to characterize this prism in order to be able to employ it later on in an analysis by shearing. A prism of Wollaston is a prism produced in a birefringent material i.e. having two indexes of refraction. This prism is cleaved so as to present the directions associated with these indices in its face with entry. It should be noted that these directions are perpendicular between them.

Keywords: non destructive control, aluminium, interferometry, treatment of image

Procedia PDF Downloads 298
900 Microglia Activity and Induction of Mechanical Allodynia after Mincle Receptor Ligand Injection in Rat Spinal Cord

Authors: Jihoon Yang, Jeong II Choi

Abstract:

Mincle is expressed in macrophages and is members of immunoreceptors induced after exposure to various stimuli and stresses. Mincle receptor activation promotes the production of these substances by increasing the transcription of inflammatory cytokines and chemokines. Cytokines, which play an important role in the initiation and maintenance of such inflammatory pain diseases, have a significant effect on sensory neurons in addition to their enhancement and inhibitory effects on immune and inflammatory cells as mediators of cell interaction. Glial cells in the central nervous system play a critical role in development and maintenance of chronic pain states. Microglia are tissue-resident macrophages in the central nervous system, and belong to a group of mononuclear phagocytes. In the central nervous system, mincle receptor is present in neurons and glial cells of the brain.This study was performed to identify the Mincle receptor in the spinal cord and to investigate the effect of Mincle receptor activation on nociception and the changes of microglia. Materials and Methods: C-type lectins(Mincle) was identified in spinal cord of Male Sprague–Dawley rats. Then, mincle receptor ligand (TDB), via an intrathecal catheter. Mechanical allodynia was measured using von Frey test to evaluate the effect of intrathecal injection of TDB. Result: The present investigation shows that the intrathecal administration of TDB in the rat produces a reliable and quantifiable mechanical hyperalgesia. In addition, The mechanical hyperalgesia after TDB injection gradually developed over time and remained until 10 days. Mincle receptor is identified in the spinal cord, mainly expressed in neuronal cells, but not in microglia or astrocyte. These results suggest that activation of mincle receptor pathway in neurons plays an important role in inducing activation of microglia and inducing mechanical allodynia.

Keywords: mincle, spinal cord, pain, microglia

Procedia PDF Downloads 137
899 Implementation of Tissue Engineering Technique to Nursing of Unhealed Diabetic Foot Lesion

Authors: Basuki Supartono

Abstract:

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

Procedia PDF Downloads 52
898 Antioxidant Potential of Pomegranate Rind Extract Attenuates Pain, Inflammation and Bone Damage in Experimental Rats

Authors: Ritu Karwasra, Surender Singh

Abstract:

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

Procedia PDF Downloads 187
897 The Effect of Probiotic and Vitamin B Complex Supplementation on Interferon-γ and Interleukin-10 Levels in Patients with TB Infection during Intensive Phase Therapy

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

Abstract:

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

Procedia PDF Downloads 354
896 Identifying Metabolic Pathways Associated with Neuroprotection Mediated by Tibolone in Human Astrocytes under an Induced Inflammatory Model

Authors: Daniel Osorio, Janneth Gonzalez, Andres Pinzon

Abstract:

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

Procedia PDF Downloads 198
895 Performance Analysis of a Planar Membrane Humidifier for PEM Fuel Cell

Authors: Yu-Hsuan Chang, Jian-Hao Su, Chen-Yu Chen, Wei-Mon Yan

Abstract:

In this work, the experimental measurement was applied to examine the membrane type and flow field design on the performance of a planar membrane humidifier. The performance indexes were used to evaluate the planar membrane humidifier. The performance indexes of the membrane humidifier include the dew point approach temperature (DPAT), water recovery ratio (WRR), water flux (J) and pressure loss (P). The experiments contain mainly three parts. In the first part, a single membrane humidifier was tested using different flow field under different dry-inlet temperatures. The measured results show that the dew point approach temperature decreases with increasing the depth of flow channel at the same width of flow channel. However, the WRR and J reduce with an increase in the dry air-inlet temperature. The pressure loss tests indicate that pressure loss decreases with increasing the hydraulic diameter of flow channel, resulting from an increase in Darcy friction. Owing to the comparison of humidifier performances and pressure losses, the flow channel of width W=1 and height H=1.5 was selected as the channel design of the multi-membrane humidifier in the second part of experiment. In the second part, the multi-membrane humidifier was used to evaluate the humidification performance under different relative humidity and flow rates. The measurement results indicate that the humidifier at both lower temperature and relative humidity of inlet dry air have higher DPAT but lower J and WRR. In addition, the counter flow approach has better mass and heat transfer performance than the parallel flow approach. Moreover, the effects of dry air temperature, relative humidity and humidification approach are not significant to the pressure loss in the planar membrane humidifier. For the third part, different membranes were tested in this work in order to find out which kind membrane is appropriate for humidifier.

Keywords: water management, planar membrane humidifier, heat and mass transfer, pressure loss, PEM fuel cell

Procedia PDF Downloads 185
894 Development of Ketorolac Tromethamine Encapsulated Stealth Liposomes: Pharmacokinetics and Bio Distribution

Authors: Yasmin Begum Mohammed

Abstract:

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

Procedia PDF Downloads 271
893 Inflammatory and Cardio Hypertrophic Remodeling Biomarkers in Patients with Fabry Disease

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

Abstract:

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

Procedia PDF Downloads 52
892 Gas Chromatography-Analysis, Antioxidant, Anti-Inflammatory, and Anticancer Activities of Some Extracts and Fractions of Linum usitatissimum

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

Abstract:

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

Procedia PDF Downloads 98
891 Amelioration of Lipopolysaccharide Induced Murine Colitis by Cell Wall Contents of Probiotic Lactobacillus Casei: Targeting Immuno-Inflammation and Oxidative Stress

Authors: Vishvas N. Patel, Mehul Chorawala

Abstract:

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

Procedia PDF Downloads 57
890 Autophagy Defects That Modify Human Immune Cell Metabolism and Promote Aging-Associated Inflammation

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

Abstract:

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

Procedia PDF Downloads 129
889 The Effect of Two Methods of Upper and Lower Resistance Exercise Training on C-Reactive Protein, Interleukin-6 and Intracellular Adhesion Molecule-1 in Healthy Untrained Women

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

Abstract:

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

Procedia PDF Downloads 224
888 Green Synthesis and Characterization of Zinc and Ferrous Nanoparticles for Their Potent Therapeutic Approach

Authors: Mukesh Saran, Ashima Bagaria

Abstract:

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

Procedia PDF Downloads 316
887 Elevated of Interleukin-6 Serum Levels in Pregnant Women with Corona Virus Disease 2019

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

Abstract:

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

Procedia PDF Downloads 33
886 Activation of NLRP3 Inflammasomes by Helicobacter pylori Infection in Innate Cellular Model and Its Correlation to IL-1β Production

Authors: Islam Nowisser, Noha Farag, Mohamed El Azizi

Abstract:

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

Procedia PDF Downloads 98
885 The Effects of Red Onion Extract (Allium ascalonicum L.) in the Pulmonary Histopathological Lesions of Layer Chickens at 47 Days Old Raised in the Battery Cage

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

Abstract:

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

Procedia PDF Downloads 417
884 Rare Case of Pyoderma Gangrenosum of the Upper Limb

Authors: Karissa A. Graham

Abstract:

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

Procedia PDF Downloads 59
883 John Cunningham Virus Interaction with Multiple Sclerosis Disease Progression

Authors: Sina Mahdavi

Abstract:

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

Procedia PDF Downloads 98
882 Citrullinated Myelin Basic Protein Mediated Inflammation in Astrocytes

Authors: Lali Shanshiashvili, Marika Chikviladze, Nino Mamulashvili, Maia Sepashvili, Nana Narmania, David Mikeladze

Abstract:

Purpose: During demyelinating inflammatory diseases and after the damage of the myelin sheet, myelin-derived proteins, including myelin basic protein (MBP), are secreted into the extracellular space. MBP shows extensive post-translational modifications, including the deimination of arginine residues. Deiminated MBP is structurally less ordered, susceptible to proteolytic attack, and more immunogenic than the unmodified one. It is hypothesized that MBP could change the inflammatory response in astrocytes. Methods: MBP was isolated and purified from bovine brain white matter. Primary astrocyte cultures were prepared from whole brains of 2-day-old Wistar rats. For evaluation of glutamate uptake/release in astrocytes following treatment of cells with MBP charge isomers, Glutamate Assay Kit was used. The expression of EAAT-2 (excitatory amino acid transporters), peroxisome proliferator-activated receptor gamma (PPAR- γ), inhibitor of nuclear factor kappa B (IkB), and high mobility group protein B1 (HMGB1) in astrocytes were assayed by Western Blot analysis. Results: This study investigated the action of deiminated isomer (C8) on the cultured primary astrocytes and compared its effects with the effects of unmodified C1 isomers. The study found that C8 and C1 MBP differently act on the uptake and release of glutamate in astrocytes: nonmodified C1 MBP increases the uptake of glutamate and does not change the release, whereas C8 decreases the release of glutamate but does not alter the uptake. Nevertheless, both isomers increased the expression of PPAR-γ and EAAT2 in the same intensity. However, immunostaining and Western Blots of cell lysates showed a decrease of IkB and increased expression of HMGB1 after the treatment of astrocytes by C8. Moreover, in the presence of C8, astrocytes release more nitric oxide than unmodified C1 isomers. Conclusion: These data suggest that the deiminated isomer of MBP evokes an inflammatory response and enhances the ability of astrocytes to release proinflammatory mediators through activation of NF-kB after the breakdown of myelin sheets. Acknowledgment: This research was supported by the SRNSF Georgia RF17_534 grant.

Keywords: myelin basic protein, glutamate, deimination, astrocytes, inflammation

Procedia PDF Downloads 175
881 Novel Molecular Mechanisms Involved in Macrophage Phenotypic Polarization

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

Abstract:

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)

Procedia PDF Downloads 255
880 Anti-Colitic and Anti-Inflammatory Effects of Lactobacillus sakei K040706 in Mice with Ulcerative Colitis

Authors: Seunghwan Seo, Woo-Seok Lee, Ji-Sun Shin, Young Kyoung Rhee, Chang-Won Cho, Hee-Do Hong, Kyung-Tae Lee

Abstract:

Doenjang, known as traditional Korean food, is product of a natural mixed fermentation process carried out by lactic acid bacteria (LAB). Lactobacillus sakei K040706 (K040706) has been accepted as the most populous LAB in over ripened doenjang. Recently, we reported the immunostimulatory effects of K040706 in RAW 264.7 macrophages and in a cyclophosphamide-induced mouse model. In this study, we investigated the ameliorative effects of K040706 in a dextran sulfate sodium (DSS)-induced colitis mouse model. We induced colitis using DSS in 5-week-ICR mice over 14 days with or without 0.1, 1 g/kg/day K040706 orally. The body weight, stool consistency, and gross bleeding were recorded for determination of the disease activity index (DAI). At the end of treatment, animals were sacrificed and colonic tissues were collected and subjected to histological experiments and myeloperoxidase (MPO) accumulation, cytokine determination, qRT-PCR and Western blot analysis. Results showed that K040706 significantly attenuated DSS-induced DAI score, shortening of colon length, enlargement of spleen and immune cell infiltrations into colonic tissues. Histological examinations indicated that K040706 suppressed edema, mucosal damage, and the loss of crypts induced by DSS. These results were correlated with the restoration of tight junction protein expression, such as, ZO-1 and occludin in K040706-treated mice. Moreover, K040706 reduced the abnormal secretions and mRNA expressions of pro-inflammatory mediators, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). DSS-induced mRNA expression of intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) in colonic tissues was also downregulated by K040706 treatment. Furthermore, K040706 suppressed the protein and mRNA expression of toll-like receptor 4 (TLR4) and phosphorylation of NF-κB and signal transducer and activator of transcription 3 (STAT3). These results suggest that K040706 has an anti-colitic effect by inhibition of intestinal inflammatory responses in DSS-induced colitic mice.

Keywords: Lactobacillus sakei, NF-κB, STAT3, ulcerative colitis

Procedia PDF Downloads 304
879 Simultaneous Targeting of MYD88 and Nur77 as an Effective Approach for the Treatment of Inflammatory Diseases

Authors: Uzma Saqib, Mirza S. Baig

Abstract:

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

Procedia PDF Downloads 278
878 Comparison of the Effect of Heart Rate Variability Biofeedback and Slow Breathing Training on Promoting Autonomic Nervous Function Related Performance

Authors: Yi Jen Wang, Yu Ju Chen

Abstract:

Background: Heart rate variability (HRV) biofeedback can promote autonomic nervous function, sleep quality and reduce psychological stress. In HRV biofeedback training, it is hoped that through the guidance of machine video or audio, the patient can breathe slowly according to his own heart rate changes so that the heart and lungs can achieve resonance, thereby promoting the related effects of autonomic nerve function; while, it is also pointed out that if slow breathing of 6 times per minute can also guide the case to achieve the effect of cardiopulmonary resonance. However, there is no relevant research to explore the comparison of the effectiveness of cardiopulmonary resonance by using video or audio HRV biofeedback training and metronome-guided slow breathing. Purpose: To compare the promotion of autonomic nervous function performance between using HRV biofeedback and slow breathing guided by a metronome. Method: This research is a kind of experimental design with convenient sampling; the cases are randomly divided into the heart rate variability biofeedback training group and the slow breathing training group. The HRV biofeedback training group will conduct HRV biofeedback training in a four-week laboratory and use the home training device for autonomous training; while the slow breathing training group will conduct slow breathing training in the four-week laboratory using the mobile phone APP breathing metronome to guide the slow breathing training, and use the mobile phone APP for autonomous training at home. After two groups were enrolled and four weeks after the intervention, the autonomic nervous function-related performance was repeatedly measured. Using the chi-square test, student’s t-test and other statistical methods to analyze the results, and use p <0.05 as the basis for statistical significance. Results: A total of 27 subjects were included in the analysis. After four weeks of training, the HRV biofeedback training group showed significant improvement in the HRV indexes (SDNN, RMSSD, HF, TP) and sleep quality. Although the stress index also decreased, it did not reach statistical significance; the slow breathing training group was not statistically significant after four weeks of training, only sleep quality improved significantly, while the HRV indexes (SDNN, RMSSD, TP) all increased. Although HF and stress indexes decreased, they were not statistically significant. Comparing the difference between the two groups after training, it was found that the HF index improved significantly and reached statistical significance in the HRV biofeedback training group. Although the sleep quality of the two groups improved, it did not reach that level in a statistically significant difference. Conclusion: HRV biofeedback training is more effective in promoting autonomic nervous function than slow breathing training, but the effects of reducing stress and promoting sleep quality need to be explored after increasing the number of samples. The results of this study can provide a reference for clinical or community health promotion. In the future, it can also be further designed to integrate heart rate variability biological feedback training into the development of AI artificial intelligence wearable devices, which can make it more convenient for people to train independently and get effective feedback in time.

Keywords: autonomic nervous function, HRV biofeedback, heart rate variability, slow breathing

Procedia PDF Downloads 146
877 Deterioration Prediction of Pavement Load Bearing Capacity from FWD Data

Authors: Kotaro Sasai, Daijiro Mizutani, Kiyoyuki Kaito

Abstract:

Expressways in Japan have been built in an accelerating manner since the 1960s with the aid of rapid economic growth. About 40 percent in length of expressways in Japan is now 30 years and older and has become superannuated. Time-related deterioration has therefore reached to a degree that administrators, from a standpoint of operation and maintenance, are forced to take prompt measures on a large scale aiming at repairing inner damage deep in pavements. These measures have already been performed for bridge management in Japan and are also expected to be embodied for pavement management. Thus, planning methods for the measures are increasingly demanded. Deterioration of layers around road surface such as surface course and binder course is brought about at the early stages of whole pavement deterioration process, around 10 to 30 years after construction. These layers have been repaired primarily because inner damage usually becomes significant after outer damage, and because surveys for measuring inner damage such as Falling Weight Deflectometer (FWD) survey and open-cut survey are costly and time-consuming process, which has made it difficult for administrators to focus on inner damage as much as they have been supposed to. As expressways today have serious time-related deterioration within them deriving from the long time span since they started to be used, it is obvious the idea of repairing layers deep in pavements such as base course and subgrade must be taken into consideration when planning maintenance on a large scale. This sort of maintenance requires precisely predicting degrees of deterioration as well as grasping the present situations of pavements. Methods for predicting deterioration are determined to be either mechanical or statistical. While few mechanical models have been presented, as far as the authors know of, previous studies have presented statistical methods for predicting deterioration in pavements. One describes deterioration process by estimating Markov deterioration hazard model, while another study illustrates it by estimating Proportional deterioration hazard model. Both of the studies analyze deflection data obtained from FWD surveys and present statistical methods for predicting deterioration process of layers around road surface. However, layers of base course and subgrade remain unanalyzed. In this study, data collected from FWD surveys are analyzed to predict deterioration process of layers deep in pavements in addition to surface layers by a means of estimating a deterioration hazard model using continuous indexes. This model can prevent the loss of information of data when setting rating categories in Markov deterioration hazard model when evaluating degrees of deterioration in roadbeds and subgrades. As a result of portraying continuous indexes, the model can predict deterioration in each layer of pavements and evaluate it quantitatively. Additionally, as the model can also depict probability distribution of the indexes at an arbitrary point and establish a risk control level arbitrarily, it is expected that this study will provide knowledge like life cycle cost and informative content during decision making process referring to where to do maintenance on as well as when.

Keywords: deterioration hazard model, falling weight deflectometer, inner damage, load bearing capacity, pavement

Procedia PDF Downloads 355
876 The Effect of Physical Exercise to Level of Nuclear Factor Kappa B on Serum, Macrophages and Myocytes

Authors: Eryati Darwin, Eka Fithra Elfi, Indria Hafizah

Abstract:

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

Procedia PDF Downloads 237
875 Effect of Probiotics and Vitamin B on Plasma Interferon-Gamma and Interleukin-6 Levels in Active Pulmonary Tuberculosis

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

Abstract:

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

Procedia PDF Downloads 322