Search results for: immune and inflammatory response

Authors: Mihai Palade, Gina Cecilia Pistol, Mariana Stancu, Veronica Chedea, Ionelia Taranu

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Nutrition is an important determinant of general health status, with especially focus on prevention and/or attenuation of the inflammatory-associated pathologies. People with chronic kidney disease can experience chronic inflammation that can lead to cardiovascular disease and even an increased rate of death. There are important links between chronic kidney diseases, inflammation and nutritional strategies that may prevent or protect against undesirable inflammation and oxidative stress. The grape by-products either seeds or pomace are rich in polyphenols which may be beneficial in prevention of inflammatory, antioxidant and antimicrobial processes. As a model for studying the impact of grape seeds on renal inflammation and oxidative stress, we used in this study weaned piglets. After a feeding trial of 30 days with a control diet and an experimental diet containing 5% grape seed (GS), kidney samples were collected. In renal tissues were determined the expression and activity of important markers of immune respose and oxidative stress: pro-inflammatory cytokines (TNF-alpha, IL-1 beta, IL-6, IL-8, IFN-gamma), anti-inflammatory cytokines (IL-4, IL-10), anti-oxidant enzymes (catalase CAT, superoxide dismutase SOD, glutathione peroxidise GPx) and important mediators belonging to nuclear receptors (NF-kB1, Nrf-2 and PPAR-gamma). Gene expression was evaluated by qPCR, whereas protein concentration was determined using proteomic techniques (ELISA). The activity of anti-oxidant enzymes was determined using specific kits. Our results showed that GS enriched in polyphenols does not have effect on TNF-alpha, IL-6 and IL-1 beta gene expression and protein concentration in kidney. By contrast, the gene expression and protein level of IL-8 and IFN-gamma were decreased in GS kidney. Anti-inflammatory cytokines IL-4 and IL-10 gene levels were increased in kidneys collected from GS piglets in comparison with controls, with no modification of protein levels between the two groups. The activities of anti-oxidant enzymes CAT and GPx were increased in kidney by GS, whereas SOD activity was unmodified in comparison with control samples. Also, the GS diet was associated with no modulation of mRNAs for nuclear receptors NF-kB1, Nrf-2 and PPAR-gamma gene expressions in kidneys. In conclusion, our results demonstrated that GS enriched in bioactive compounds such polyphenols could modulate inflammation and oxidative stress markers in kidney tissues. Further studies are necessary to elucidate the mechanism of action of GS compounds in case kidney inflammation associated with oxidative stress, and signalling molecules involved in these mechanisms.

Keywords: animal model, kidney inflammation, oxidative stress, grape seed

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Authors: Mohamed Hendawy Mousa, Warda Youssef Mohamed Morsy

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Background: Sepsis is a major cause of mortality and morbidity in trauma patients. Body mass index as an indicator of nutritional status was reported as a predictor of injury pattern and complications among critically ill injured patients. Aim: The aim of this study is to investigate the relationship between body mass index and the development of sepsis, systemic inflammatory response syndrome among adult trauma patients at emergency hospital - Cairo University. Research design: Descriptive correlational research design was utilized in the current study. Research questions: Q1. What is the body mass index profile of adult trauma patients admitted to the emergency hospital at Cairo University over a period of 6 months?, Q2. What is the frequency of systemic inflammatory response syndrome and sepsis among adult trauma patients admitted to the emergency hospital at Cairo University over a period of 6 months?, and Q3. What is the relationship between the development of sepsis, systemic inflammatory response syndrome and body mass index among adult trauma patients admitted to the emergency hospital at Cairo University over a period of 6 months?. Sample: A purposive sample of 52 adult male and female trauma patients with revised trauma score 10 to 12. Setting: The Emergency Hospital affiliated to Cairo University. Tools: Four tools were utilized to collect data pertinent to the study: Socio demographic and medical data tool, Systemic inflammatory response syndrome assessment tool, Revised Trauma Score tool, and Sequential organ failure assessment tool. Results: The current study revealed that, (61.5 %) of the studied subjects had normal body mass index, (25 %) were overweight, and (13.5 %) were underweight. 84.6% of the studied subjects had systemic inflammatory response syndrome and 92.3% were suffering from mild sepsis. No significant statistical relationship was found between body mass index and occurrence of Systemic inflammatory response syndrome (2= 2.89 & P = 0.23). However, Sequential organ failure assessment scores were affected significantly by body mass index was found mean of initial and last Sequential organ failure assessment score for underweight, normal and obese where t= 7.24 at p = 0.000, t= 16.49 at p = 0.000 and t= 9.80 at p = 0.000 respectively. Conclusion: Underweight trauma patients showed significantly higher rate of developing sepsis as compared to patients with normal body weight and obese. Recommendations: based on finding of this study the following are recommended: replication of the study on a larger probability sample from different geographical locations in Egypt; Carrying out of further studies in order to assess the other risk factors influencing trauma outcome and incidence of its complications; Establishment of standardized guidelines for managing underweight traumatized patients with sepsis.

Keywords: body mass index, sepsis, systemic inflammatory response syndrome, adult trauma

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Authors: Rahul Madathiparambil Visalakshan, Alex Cavallaro, John Hayball, Krasimir Vasilev

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The role of biomaterial surface nanotopograhy on fibrinogen adsorption and unfolding, and the subsequent immune response were studied. Inconsistent topography and varying chemical functionalities along with a lack of reproducibility pose a challenge in determining the specific effects of nanotopography or chemistry on proteins and cells. It is important to have a well-defined nanotopography with a homogeneous chemistry to study the real effect of nanotopography on biological systems. Therefore, we developed a technique that can produce well-defined and highly reproducible topography to identify the role of specific roughness, size, height and density with the presence of homogeneous chemical functionality. Using plasma polymerisation of oxazoline monomers and immobilized gold nanoparticles we created surfaces with an equal number density of nanoparticles of different sizes. This surface was used to study the role of surface nanotopography and the interplay of surface chemistry on proteins and immune cells. The effect of nanotopography on fibrinogen adsorption was investigated using Quartz Cristal Microbalance with Dissipation and micro BCA. The mass of fibrinogen adsorbed on the surface increased with increasing size of nano-topography. Protein structural changes up on adsorption to the nano rough surface was studied using circular dichroism spectroscopy. Fibrinogen unfolding varied depending on the specific nanotopography of the surfaces. It was revealed that the in vitro immune response to the nanotopography surfaces changed due to this protein unfolding.

Keywords: biomaterial inflammation, protein and cell responses, protein unfolding, surface nanotopography

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Authors: Zoe Goldberger, Priscilla S. Briquez, Jeffrey A. Hubbell

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Tumor cells have mutations resulting from genetic instability that the immune system can actively recognize. Immune checkpoint immunotherapy (ICI) is commonly used in the clinic to re-activate immune reactions against mutated proteins, called neoantigens, resulting in tumor remission in cancer patients. However, only around 20% of patients show durable response to ICI. While tumor mutational burden (TMB) has been approved by the Food and Drug Administration (FDA) as a criterion for ICI therapy, the relevance of the subcellular localizations of the mutated proteins within the tumor cell has not been investigated. Here, we hypothesized that localization of mutations impacts the effect of immune responsiveness to ICI. We analyzed publicly available tumor mutation sequencing data of ICI treated patients from 3 independent datasets. We extracted the subcellular localization from the UniProtKB/Swiss-Prot database and quantified the proportion of membrane, cytoplasmic, nuclear, or secreted mutations per patient. We analyzed this information in relation to response to ICI treatment and overall survival of patients showing with 1722 ICI-treated patients that high mutational burden localized at the membrane (mTMB), correlate with ICI responsiveness, and improved overall survival in multiple cancer types. We anticipate that our results will ameliorate predictability of cancer patient response to ICI with potential implications in clinical guidelines to tailor ICI treatment. This would not only increase patient survival for those receiving ICI, but also patients’ quality of life by reducing the number of patients enduring non-effective ICI treatments.

Keywords: cancer, immunotherapy, membrane neoantigens, efficacy prediction, biomarkers

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Authors: Kumari Rekha, Mathur K Dhananjay, Maheshwari Deepanshu, Nautiyal Nidhi, Shubham Smriti, Laal Deepika, Sinha Swati, Kumar Anupam, Biswas Subhrajit, Shiv Kumar Sarin

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Background: Mesenchymal stem cells are multipotent stem cells derived from mesoderm and are used for therapeutic purposes because of their self-renewal, homing capacity, Immunomodulatory capability, low immunogenicity and mitochondrial transfer signaling. MSCs have the ability to regulate the mechanism of both innate as well as adaptive immune responses through the modulation of cellular response and the secretion of inflammatory mediators. Different sources of MSC are UC MSC, BM MSC, Dental Pulp, and Adipose MSC. The most frequent source used is umbilical cord tissue due to its being easily available and free of limitations of collection procedures from respective hospitals. The immunosuppressive role of MSCs is particularly interesting for clinical use since it confers resistance to rejection by the host immune response. Methodology: In this study, T helper cells (TH4), Cytotoxic T cells (CD-8), immunoregulatory cells (CD25 +FOXP3+) are compared from isolated MSC from three different methods, UC Dissociation Kit (Miltenyi), Explant Culture and Collagenase Type-IV. To check the immunomodulatory property, these MSCs were seeded with PBMC(Coculture) in CD3 coated 24 well plates. Cd28 antibody was added in coculture for six days. The coculture was analyzed in FACS Verse flow cytometry. Results: From flow cytometry analysis of coculture, it found that All over T helper cells (CD4+) number p<0.0264 increases in (All Enzymes) MSC rather than explant MSC(p>0.0895) as compared to Collagenase(p>0.7889) in a coculture of Activated T cell and Mesenchymal Stem Cell. Similar T reg cells (CD25+, FOXP3+) expression p<0.0234increases in All Enzymes), decreases in Explant and Collagenase. Experiments have shown that MSCs can also directly prevent the cytotoxic activity of CD8 lymphocytes mainly by blocking their proliferation rather than by inhibiting the cytotoxic effect. And promoting the t-reg cells, which helps in the mediation of immune response in various diseases. Conclusion: MSC suppress Cytotoxic CD8 T cell and Enhance immunoregulatory T reg (CD4+, CD25+, FOXP3+) Cell expression. Thus, MSC maintains a proper balance(ratio) between CD4 T cells and Cytotoxic CD8 T cells.

Keywords: MSC, disease, T cell, T regulatory

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Authors: Q. B. Maria de la Luz Ortega Juárez, Saúl Rojas Hernández, Itzel Berenice Rodríguez Mera, María Maricela Carrasco Yépez, Mara Gutierrez Sánchez

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Naegleria fowleri is a free-living amoeba found mainly in temperate freshwater and is the etiologic agent of primary amebic meningoencephalitis (PAM), a fatal acute disease with a mortality rate greater than 95%. At present, there are no treatments available for MAP, and the development of effective vaccines that generate long-term immunological memory allowing protection against MAP would be of great importance. The objective of this work was to analyze the effector and memory immune response in BALB/c mice immunized with total extract of N. fowleri co-administered with cholera toxin. In this study, BALB/c mice were immunized four times intranasally with ET of N. fowleri adjuvanted with CT with or without booster at three months and were challenged or not with the lethal dose of N. fowleri, determining survival, the humoral, effector and memory response, by ELISA and flow cytometry techniques. The results obtained showed that the survival of mice immunized with booster had 60% protection compared to the group without booster, which obtained 20% protection. Evaluating the humoral response, it was found that both IgG and IgA levels were higher in sera than in nasal washes in both treatments. In the cellular response, the increase in the percentage of positive cells was found for effector T and B lymphocytes in the nasal passages (NP) in the group with boost and nasopharynx-associated lymphoid tissue (NALT) in the group without boost and lymphocytes only. B in both treatments, as well as in memory cells treatment with boost T lymphocytes in PN and NALT and without boost in cervical lymph nodes (CG) with respect to B lymphocytes, in PN, GC and NALT in treatment with boost and NALT in treatment without booster. Therefore, the involvement of the effector immune response and memory play a fundamental role for protection against N. fowleri and for the development of vaccine candidates.

Keywords: immune response, immunological memory, naegleria fowleri, primary amebic meningoencephalitis

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Authors: Ankita Singh, Chandan Gorain, Amirul I. Mallick

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Successful adherence of the mucosal epithelial cells is the key early step for Campylobacter jejuni pathogenesis (C. jejuni). A set of Surface Exposed Colonization Proteins (SECPs) are among the major factors involved in host cell adherence and invasion of C. jejuni. Among them, constitutively expressed surface-exposed lipoprotein adhesin of C. jejuni, JlpA, interacts with intestinal heat shock protein 90 (hsp90α) and contributes in disease progression by triggering pro-inflammatory response via activation of NF-κB and p38 MAP kinase pathway. Together with its ability to express in the bacterial surface, higher sequence conservation and predicted predominance of several B cells epitopes, JlpA protein reserves its potential to become an effective vaccine candidate against wide range of Campylobacter sps including C. jejuni. Given that chickens are the primary sources for C. jejuni and persistent gut colonization remain as major cause for foodborne pathogenesis to humans, present study explicitly used chickens as model to test the immune-protective efficacy of JlpA protein. Taking into account that gastrointestinal tract is the focal site for C. jejuni colonization, to extrapolate the benefit of mucosal (intragastric) delivery of JlpA protein, a food grade Nisin inducible Lactic acid producing bacteria, Lactococcus lactis (L. lactis) was engineered to express recombinant JlpA protein (rJlpA) in the surface of the bacteria. Following evaluation of optimal surface expression and functionality of recombinant JlpA protein expressed by recombinant L. lactis (rL. lactis), the immune-protective role of intragastric administration of live rL. lactis was assessed in commercial broiler chickens. In addition to the significant elevation of antigen specific mucosal immune responses in the intestine of chickens that received three doses of rL. lactis, marked upregulation of Toll-like receptor 2 (TLR2) gene expression in association with mixed pro-inflammatory responses (both Th1 and Th17 type) was observed. Furthermore, intragastric delivery of rJlpA expressed by rL. lactis, but not the injectable form, resulted in a significant reduction in C. jejuni colonization in chickens suggesting that mucosal delivery of live rL. lactis expressing JlpA serves as a promising vaccine platform to induce strong immune-protective responses against C. jejuni in chickens.

Keywords: chickens, lipoprotein adhesion of Campylobacter jejuni, immuno-protection, Lactococcus lactis, mucosal delivery

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Authors: Seyedahmad Hosseini, Mohammadjavad Sotoudeheian

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Introduction: Allergic asthma is a heterogeneous immuno-inflammatory disease based on Th-2-mediated inflammation. Histopathologic abnormalities of the airways characteristic of asthma include epithelial damage and subepithelial collagen deposition. Objectives: Human bronchial epithelial cell genome expression of TNF‑α, IL‑6, ICAM‑1, VCAM‑1, nuclear factor (NF)‑κB signaling pathways up-regulate during inflammatory cascades. Moreover, immunofluorescence assays confirmed the nuclear translocation of NF‑κB p65 during inflammatory responses. An absolute LDH leakage assays suggestedLPS-inducedcells injury, and the associated mechanisms are co-incident events. LPS-induced phosphorylation of ERKand JNK causes inflammation in epithelial cells through inhibition of ERK and JNK activation and NF-κB signaling pathway. Furthermore, the inhibition of NF-κB mRNA expression and the nuclear translocation of NF-κB lead to anti-inflammatory events. Likewise, activation of SUMF2 which inhibits IL-13 and reduces Th2-cytokines, NF-κB, and IgE levels to ameliorate asthma. On the other hand, TNFα-induced mucus production reduced NF-κB activation through inhibition of the activation status of Rac1 and IκBα phosphorylation. In addition, bradykinin B2 receptor (B2R), which mediates airway remodeling, regulates through NF-κB. Bronchial B2R expression is constitutively elevated in allergic asthma. In addition, certain NF-κB -dependent chemokines function to recruit eosinophils in the airway. Besides, bromodomain containing 4 (BRD4) plays a significant role in mediating innate immune response in human small airway epithelial cells as well as transglutaminase 2 (TG2), which is detectable in saliva. So, the guanine nucleotide-binding regulatory protein α-subunit, Gα16, expresses a κB-driven luciferase reporter. This response was accompanied by phosphorylation of IκBα. Furthermore, expression of Gα16 in saliva markedly enhanced TNF-α-induced κB reporter activity. Methods: The applied method to form NF-κB activation is the electromobility shift assay (EMSA). Also, B2R-BRD4-TG2 complex detection by immunoassay method within saliva with EMSA of NF-κB activation may be a novel biomarker for asthma diagnosis and follow up. Conclusion: This concept introduces NF-κB signaling pathway as potential asthma biomarkers and promising targets for the development of new therapeutic strategies against asthma.

Keywords: NF-κB, asthma, saliva, T-helper

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Authors: D. Nagalakshmi, S. Parashuramulu K. Sadasiva Rao, G. Aruna, L. Vikram

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The zinc (Zn) is the second most abundant trace element in mammals and birds, forming structural component of over 300 enzymes, playing an important role in anti-oxidant defense, immune response and reproduction. Organic trace minerals are more readily absorbed from the digestive tract and more biologically available compared with its inorganic salt. Thus, the present study was undertaken on 60 adult female Sprague Dawley rats (275±2.04 g) for experimental duration of 12 weeks to investigate the effect of dietary Zn supplementation from various organic sources on immunity, reproduction, oxidative defense mechanism and blood biochemical profile. The rats were randomly allotted to 30 replicates (2 per replicate) which were in turn randomly allotted to 5 dietary treatments varying in Zn source i.e., one inorganic source (Zn carbonate) and 4 organic sources (Zn-proteinate, Zn-propionate, Zn-amino acid complex and Zn-methionine) so as to supply NRC recommended Zn concentration (12 ppm Zn). Supplementation of organic Zn had no effect on various haematological and serum biochemical constituents compared to inorganic Zn fed rats. The TBARS and protein carbonyls concentration in liver indicative of oxidative stress was comparable between various organic and inorganic groups. The glutathione reductase activity in haemolysate (P<0.05) and reduced glutathione concentration in liver (P<0.01) was higher when fed organic Zn and RBC catalase activity was higher (P<0.01) on Zn methionine compared to other organic sources tested and the inorganic source. The humoral immune response assessed as antibody titres against sheep RBC was higher (P<0.05) when fed organic sources of zinc compared to inorganic source. The cell mediated immune response expressed as delayed type hypersensitivity reaction was higher (P<0.05) in rats fed Zn propionate with no effect of other organic Zn sources. The serum progesterone concentration was higher (P<0.05) in rats fed organic Zn sources compared to inorganic zinc. The data on ovarian folliculogenesis indicated that organic Zn supplementation increased (P<0.05) the number of graafian follicles and corpus luteum with no effect on primary, secondary and tertiary follicle number. The study indicated that rats fed organic sources of Zn had higher antioxidant enzyme activities, immune response and serum progesterone concentration with higher number of mature follicles. Though the effect of feeding various organic sources were comparable, rats fed zinc methionine had higher antioxidant activity and cell mediated immune response was higher in rats on Zn propionate.

Keywords: organic zinc, immune, rats, reproductive

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Authors: Abu Salim Mustafa

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Rv3873 is a relatively large size protein (371 amino acids in length) and its gene is located in the immunodominant genomic region of difference (RD)1 that is present in the genome of Mycobacterium tuberculosis but deleted from the genomes of all the vaccine strains of Bacillus Calmette Guerin (BCG) and most other mycobacteria. However, when tested for cellular immune responses using peripheral blood mononuclear cells from tuberculosis patients and BCG-vaccinated healthy subjects, this protein was found to be a major stimulator of cell mediated immune responses in both groups of subjects. In order to further identify the sequence of immunodominant epitopes and explore their Human Leukocyte Antigen (HLA)-restriction for epitope recognition, 24 peptides (25-mers overlapping with the neighboring peptides by 10 residues) covering the sequence of Rv3873 were synthesized chemically using fluorenylmethyloxycarbonyl chemistry and tested in cell mediated immune responses. The results of these experiments helped in the identification of an immunodominant peptide P9 that was recognized by people expressing varying HLA-DR types. Furthermore, it was also predicted to be a promiscuous binder with multiple epitopes for binding to HLA-DR, HLA-DP and HLA-DQ alleles of HLA-class II molecules that present antigens to T helper cells, and to HLA-class I molecules that present antigens to T cytotoxic cells. In addition, the evaluation of peptide P9 using an immunogenicity predictor server yielded a high score (0.94), which indicated a greater probability of this peptide to elicit a protective cellular immune response. In conclusion, P9, a peptide with multiple epitopes and ability to bind several HLA class I and class II molecules for presentation to cells of the cellular immune response, may be useful as a peptide-based vaccine against tuberculosis.

Keywords: mycobacterium tuberculosis, PPE68, peptides, vaccine

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Authors: Sourav Ghosh, Antony Gomes

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

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

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Authors: Dandan Shen, Hui-zhu Wang, Xi Yu, LiLi Gui, Xiao Wei, Xiao-yan Jiang, Da-wei Wang, Min Hong

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Yu-ping-feng-san (YPFS) is a clinical medicine for asthma and other allergic diseases, but the mechanism of YPFS on relapse of allergy is unclear. Currently, people come to realize the epithelial cells(EC) play a key role in stimulating and regulating local immune response. The study of thymic stromal lymphopoietin（TSLP derived from EC provides an important evidence that the EC can regulate immune response to stimulate allergic response. In this study, we observed the effect of YPFS on TSLP in vivo and in vitro. We established a method by using bronchial epithelial cells (16HBE) for screening potential bioactive components by HPLC-MS in YPFS and then analyzed the components in serum containing YPFS by UPLC-MS. The results showed that YPFS could decrease TSLP protein level in OVA-sensitized mice and 16HBE cells. Five components combing with the 16HBE cells were both detected in the serum.

Keywords: TSLP, bronchial epithelial cells, cell-binding, drug-containing serum

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Authors: Hanan Begali, Shahi Dost, Annett Ziegler, Markus Cornberg, Maria-Esther Vidal, Anke R. M. Kraft

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Chronic hepatitis B virus (HBV) infection can be treated with nucleot(s)ide analog (NA), for example, which inhibits HBV replication. However, they have hardly any influence on the functional cure of HBV, which is defined by hepatitis B surface antigen (HBsAg) loss. NA needs to be taken life-long, which is not available for all patients worldwide. Additionally, NA-treated patients are still at risk of developing cirrhosis, liver failure, or hepatocellular carcinoma (HCC). Although each patient has the same components of the immune system, immune responses vary between patients. Therefore, a deeper understanding of the immune response against HBV in different patients is necessary to understand the parameters leading to HBV cure and to use this knowledge to optimize HBV therapies. This requires seamless integration of an enormous amount of diverse and fine-grained data from viral markers, e.g., hepatitis B core-related antigen (HBcrAg) and hepatitis B surface antigen (HBsAg). The data integration system relies on the assumption that profiling human immune systems requires the analysis of various variables (e.g., demographic data, treatments, pre-existing conditions, immune cell response, or HLA-typing) rather than only one. However, the values of these variables are collected independently. They are presented in a myriad of formats, e.g., excel files, textual descriptions, lab book notes, and images of flow cytometry dot plots. Additionally, patients can be identified differently in these analyses. This heterogeneity complicates the integration of variables, as data management techniques are needed to create a unified view in which individual formats and identifiers are transparent when profiling the human immune systems. The proposed study (HBsRE) aims at integrating heterogeneous data sets of 87 chronically HBV-infected patients, e.g., clinical data, immune cell response, and HLA-typing, with knowledge encoded in biomedical ontologies and open-source databases into a knowledge-driven framework. This new technique enables us to harmonize and standardize heterogeneous datasets in the defined modeling of the data integration system, which will be evaluated in the knowledge graph (KG). KGs are data structures that represent the knowledge and data as factual statements using a graph data model. Finally, the analytic data model will be applied on top of KG in order to develop a deeper understanding of the immune profiles among various patients and to evaluate factors playing a role in a holistic profile of patients with HBsAg level loss. Additionally, our objective is to utilize this unified approach to stratify patients for new effective treatments. This study is developed in the context of the project “Transforming big data into knowledge: for deep immune profiling in vaccination, infectious diseases, and transplantation (ImProVIT)”, which is a multidisciplinary team composed of computer scientists, infection biologists, and immunologists.

Keywords: chronic hepatitis B infection, immune response, knowledge graphs, ontology

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Authors: Lea Boidin, Martha Baydoun, Bertrand Leroux, Olivier Morales, Samir Acherar, Celine Frochot, Nadira Delhem

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Ovarian cancer (OC) is one of the most defying diseases in gynecologic oncology. Even though surgery remains crucial in the therapy of patients with primary ovarian cancer, recurrent recidivism calls for the development of new therapy protocols to propose for patients dealing with this cancer. FRα is described as a tumor‐associated antigen in OC, where FRα expression is usually linked with more poorly differentiated, aggressive tumors. The Photodynamic treatment (PDT) available data have shown improvements in the uptake of small tumors and in the induction of a proper anti-tumoral immune response. In order to target specifically peritoneal metastatis, which overexpress FRα, a new-patented PS coupled with folic acid has been developed in our team. Herein we propose PDT using this new patented PS for PDT applied in an in vivo mice model. The efficacy of the treatment was evaluated in mice without and with PBMC reconstitution. Mice were divided into four groups: Non-Treated, PS, Light Only, and PDT Treated and subjected to illumination by laser set at 668nm with a duration of illumination of 45 minutes (or 1 min of illumination followed by 2 minutes of pause repeated 45 times). When mice were not reconstituted and after fractionized PDT protocol, a significant decrease in the tumor volume was noticed. An induction in the anti-tumoral cytokine IFNγ chaperoned this decrease while a subsequent inhibition in the cytokine TGFβ. Even more crucial, when mice were reconstituted and upon PDT, the fold of tumor decrease was even higher. An immune response was activated decoded with an increase in NK, CD3 +, LT helper and Cytotoxic T cells. Thereafter, an increase in the expression of the cytokines IFNγ and TNFα were noticed while an inhibition in TGFβ, IL8 and IL10 accompanied this immune response activation. Therefore, our work has shown for the first time that a fractionized PDT protocol using a folate-targeted PDT is effective for treatment of ovarian cancer. The interest in using PDT in this case, goes beyond the local induction of tumor apoptosis only, but can promote subsequent anti-tumor response. Most of the therapies currently used to treat ovarian cancer, have an uncooperative outcomes on the host immune response. The readiness of a tumor adjuvant treatment like PDT adequate in eliminating the tumor and in concert stimulating anti-tumor immunity would be weighty.

Keywords: folate receptor, ovarian cancer, photodynamic therapy, humanized mice model

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Authors: M. A. Ferhat, M. N. Boukhatem, F. Chemat

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Since the available anti-inflammatory drugs exert an extensive variety of side effects, the search for new anti-inflammatory agents has been a priority of pharmaceutical industries. The aim of the present study was to assess the anti-inflammatory activities of the essential oil of rose geranium (RGEO). The chemical composition of the RGEO was investigated by gas chromatography. The major components were citronellol (29.13%), geraniol (12.62%), and citronellyl formate (8.06%). In the carrageenan induced paw edema, five different groups were established and RGEO was administered orally in three different doses. RGEO (100 mg/kg) was able to significantly reduce the paw edema with a comparable effect to that observed with diclofenac, the positive control. In addition, RGEO showed a potent anti-inflammatory activity by topical treatment in the method of croton oil-induced ear edema. When the dose was 5 or 10 ml of RGEO per ear, the inflammation was reduced by 73 and 88%, respectively. This is the first report to demonstrate a significant anti-inflammatory activity of Algerian RGEO. In addition, histological analysis confirmed that RGEO inhibited the inflammatory responses in the skin. Our results indicate that RGEO may have significant potential for the development of novel anti-inflammatory drugs with improved safety profile.

Keywords: anti-inflammatory effect, carrageenan, citronellol, histopathology, Rose geranium

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Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

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Kawasaki disease (KD) is the primary cause of acquired pediatric heart disease as an acute vasculitis. In children with prolonged fever, rash, and inflammation of the mucosa KD must be considered as a clinical diagnosis. There is a persuasive suggestion of immune-mediated damage as the pathophysiologic cascade of KD. For example, the invasion of cytotoxic T-cells supports a viral etiology and the inflammasome of the innate immune system is a critical component in the vasculitis formation in KD. Animal models of KD propose the cytokine profiles, such as increased IL-1 and GM-CSF, which cause vascular damage. CRP and IFN-γ elevated expression and the upregulation of IL-6, and IL-10 production are also described in previous studies. Untreated KD is a critical risk factor for coronary artery diseases and myocardial infarction. Vascular damage may encompass amplified T-cell activity. SMAD3 is an essential molecule in down-regulating T-cells and increasing expression of FoxP3. It has a critical effect in the differentiation of regulatory T-cells. The discrepancy of regulatory T-cells and pro-inflammatory Th17 has been studied in acute coronary syndrome during KD. However in the coronary artery damaged lymphocytes and IgA plasma cells are seen at the lesion locations, the major immune cells in the coronary lesions are monocytes/macrophages and neutrophils. These cells secrete TNF-α, and activates matrix metalloprotease (MMP)-9, reducing the integrity of vessels and prompting patients to arise aneurysm. MMPs can break down the components of the extracellular matrix and assist immune cell movement. IVIG as an effective form of treatment clarified the role of the immune system, which may target pathogenic antigens and regulate cytokine production. Several reports have revealed that in the coronary arteries, high expression of MMP-9 in monocyte/macrophage results in pathologic cascades. Curcumin is a potent antioxidant and anti-inflammatory molecule. Curcumin decreases the production of reactive oxygen and nitrogen species and inhibits transcription factors like AP-1 and NF-κB. Curcumin also contains the characteristics of inhibitory effects on MMPs, especially MMP-9. The upregulation of MMP-9 is an important cellular response. Curcumin treatment caused a reverse effect and down-regulates MMP-9 gene expression which may fund the anti-inflammatory effect. Curcumin inhibits MMP-9 expression via PKC and AMPK-dependent pathways in Human monocytes cells. Elevated expression and activity of MMP-9 are correlated with advanced vascular lesions. AMPK controls lipid metabolism and oxidation, and protein synthesis. AMPK is also necessary for the MMP-9 activity and THP-1 cell adhesion to endothelial cells. Curcumin was shown to inhibit the activation of AMPKα. Compound C (AMPK inhibitor) inhibits MMP-9 expression level. Therefore, through inactivating AMPKs and PKC, curcumin decreases the MMP-9 level, which results in inhibiting monocyte/macrophage differentiation. Compound C also suppress the phosphorylation of three major classes of MAP kinase signaling, suggesting that curcumin may suppress MMP-9 level by inactivation of MAPK pathways. MAPK cascades are activated to induce the expression of MMP-9. Curcumin inhibits MAPKs phosphorylation, which contributes to the down-regulation of MMP-9. This study demonstrated that the potential inhibitory properties of curcumin over MMP-9 lead to a therapeutic strategy to reduce the risk of coronary artery involvement during KD.

Keywords: MMP-9, coronary artery aneurysm, Kawasaki’s disease, curcumin, AMPK, immune system, NF-κB, MAPK

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Authors: Mudassar Hameed, Khushi Muhammad, Aamir Ghafoor, Masood Rabbani, Momena Habib, Jawad Nazir

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Comparative efficacy of three formulations (non-adjuvant, gel, and oil adjuvant) of monovalent and combined PPR and FMD virus vaccines was evaluated in goats. All kinds of monovalent PPRV vaccines elicited protective antibody titers at one-month post vaccination (PV) that remained so till six months PV. Monovalent non-adjuvant (NA) FMDV vaccine provoked non-protective antibody titers that declined to undetectable levels after three months. In case of combined vaccines, all of the formulations elicited protective antibody titers against PPRV in vaccinated animals which remained above that limit for six months. However, an exceptional immune response against FMDV was observed in combined NA vaccine group where antibody titers were extremely high and remained above protective level till 4 months PV in animals who received a single vaccine shot and till six months PV in booster group. Although, adjuvant or NA combined vaccines can induce protective antibody titers against both of the viruses within one month PV, but a booster vaccine shot is needed to retain protective antibody level for 6 months duration. Immune response elicited by combined vaccines is comparable or superior to the monovalent vaccines. Hence combined vaccine can be effectively used for the control and prevention of both of the diseases.

Keywords: antibody titer, protective, combined vaccine, non adjuvant

Procedia PDF Downloads 179

Authors: Connick K, Lalor R, Murphy A, O’Neill S. M., Rabab S. Zalat, Eman E. El Shanawany

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Cryptosporidium parvum is an opportunistic intracellular parasite that causes mild to severe diarrhea in human and animal populations and is an important zoonotic disease globally. In immunocompromised hosts, infection Canbe life-threatening as no effective treatments are currently available to control infection. To increase our understanding of the mechanisms that play a role in host-parasite interactions at the level of the immune response, we investigated the effects of Cryptosporidium parvum antigen (CPA) on bone marrow-derived (DCS). Herein we examined cytokine secretion and cell surface marker expression on DCs exposed to CPA. We also measured cytokine production in CD4+ cells co-cultured with CPA primed DCs in the presence of anti-CD3. CPA induced a significant increase in the production of interleukin(IL)-12p40, IL-10, IL-6, and TNF-α by DCs and enhanced the expression of the cell surface markers TLR4, CD80, CD86, and MHC11. CPA primed DC co-cultured in the presence of anti-CD3 with CD4+ T-cells inhibited the secretion of Th2 associated cytokines, notably IL-5 and IL-13, with no effects on the secretions of interferon (IFN)-γ, IL-2, IL-17, and IL-10. These findings support studies in the literature that CPA can induce the full maturation of DCs that subsequently initiate Th1 immune responses critical to the resolution of C. parvum infection.

Keywords: cryptosporidium parvum, dendritic cells, IL-12 p70, cell surface marker

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Authors: Tanveer Hussain, Misbah Hussain, Masroor Ellahi Babar, Muhammad Traiq Pervez, Fiaz Hussain, Sana Zahoor, Rashid Saif

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Interleukin 2 (IL-2) is a cytokine which is produced by activated T cells, play important role in immune response against antigen. It act in both autocrine and paracrine manner. It can stimulate B cells and various other phagocytic cells like monocytes, lymphokine-activated killer cells and natural killer cells. Acting in autocrine fashion, IL-2 protein plays a crucial role in proliferation of T cells. IL-2 triggers the release of pro and anti- inflammatory cytokines by activating several pathways. In present study, exon 1 of IL-2 gene of four local Pakistani breeds (Dera Din Panah, Beetal, Nachi and Kamori) from two provinces was amplified by using reported Ovine IL-2 primers, yielding PCR product of 501 bp. The sequencing of all samples was done to identify the polymorphisms in amplified region of IL-2 gene. Analysis of sequencing data resulted in identification of one novel nucleotide substitution (T→A) in amplified non-coding region of IL-2 gene. Comparison of IL-2 gene sequence of all four breeds with other goat breeds showed high similarity in sequence. While phylogenetic analysis of our local breeds with other mammals showed that IL-2 is a variable gene which has undergone many substitutions. This high substitution rate can be due to the decreased or increased changed selective pressure. These rapid changes can also lead to the change in function of immune system. This pioneering study of Pakistani goat breeds urge for further studies on immune system of each targeted breed for fully understanding the functional role of IL-2 in goat immunity.

Keywords: interleukin 2, mutational analysis, phylogeny, goat breeds, Pakistan

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Authors: K. Żak, S. Przetocka, R. Kitel, K. Guzik, B. Musielak, S. Malicki, G. Dubin, T. A. Holak

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Studies on tumor genesis revealed a number of factors that may potentially serve as molecular targets for immunotherapies. One of such promising targets are PD1 and PDL1 proteins. PD1 (Programmed cell death protein 1) is expressed by activated T cells and plays a critical role in modulation of the host's immune response. One of the PD1 ligands -PDL1- is expressed by macrophages, monocytes and cancer cells which exploit it to avoid immune attack. The notion of the mechanisms used by cancer cells to block the immune system response was utilized in the development of therapies blocking PD1-PDL1 interaction. Up to date, human PD1-PDL1 complex has not been crystallized and structure of the mouse-human complex does not provide a complete view of the molecular basis of PD1-PDL1 interactions. The purpose of this study is to obtain crystal structure of the human PD1-PDL1 complex which shall allow rational design of small molecule inhibitors of the interaction. In addition, the study presents results of binding small-molecules to PD1 and fragment docking towards PD1 protein which will facilitate the design and development of small–molecule inhibitors of PD1-PDL1 interaction.

Keywords: PD1, PDL1, cancer, small molecule, drug discovery

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Authors: Dani Sukkar, Ali Kanso, Philippe Laval-Gilly, Jairo Falla-Angel

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The honeybees' immune system is challenged by different risk factors that induce various responses. However, complex scenarios where bees are exposed to different pesticides simultaneously with immune activation are not well evaluated. The Toll pathway is one of the main signaling pathways studied in invertebrate immune responses, and it is a good indicator of the effect of such complex interactions in addition to key signaling elements of other pathways like Relish of the immune deficiency (IMD) pathway or Eater, the phagocytosis receptor or vitellogenin levels. Honeybee hemocytes extracted from 5th instar larvae were exposed to imidacloprid and/or amitraz with or without the presence of the zymosan a as an immune activator. The gene expression of multiple immune related genes were studied, including spaetzle, Toll, myD88, relish, eater and vitellogenin, by real-time polymerase chain reaction after RNA extraction. The results demonstrated that the Toll pathway is mainly affected by the pesticides; imidacloprid and amitraz, especially by their different combinations. Furthermore, immune activation by zymosan A, a fungal cell-wall component, acts to mitigate to some extent the effect of pesticides on the different levels of the Toll pathway. In addition, imidacloprid, amitraz, and zymosan A have complex and context-specific interactions depending on the levels of immune activation and the pathway evaluated affecting immune-gene expression differently.

Keywords: toll pathway, immune modulation, β-glucan, imidacloprid, amitraz, honeybees, immune genes

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Authors: Sina Mahdavi

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Background and Objective: Multiple sclerosis (MS) is an inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially Human Herpesvirus 6 (HHV-6), and MS is one potential cause that is not well understood. In this study, we aim to summarize the available data on HHV-6 infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis", " Human Herpesvirus 6 ", and "central nervous system" in the databases PubMed and Google Scholar between 2017 and 2022 were searched, and 12 articles were chosen, studied, and analyzed. Results: HHV 6 tends towards TCD 4+ lymphocytes and enters the CNS due to the weakening of the blood-brain barrier due to inflammatory damage. Following the observation that the HHV-6 U24 protein has a seven amino acid sequence with myelin basic protein, which is one of the main components of the myelin sheath, it could cause a molecular mimicry mechanism followed by cross-reactivity. Reactivation of HHV-6 in the CNS can cause the release of proinflammatory cytokines, including TNF-α, leading to immune-mediated demyelination in patients with MS. Conclusion: There is a high expression of endogenous retroviruses during the course of MS, which indicates the relationship between HHV-6 and MS, and that this virus can play a role in the development of MS by creating an inflammatory state. Therefore, measures to modulate the expression of HHV-6 may be effective in reducing inflammatory processes in demyelinated areas of MS patients.

Keywords: multiple sclerosis, human herpesvirus 6, central nervous system, autoimmunity

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Authors: Deepa Gandhi, Pravin K. Naoghare, Amit Bafana, Krishnamurthi Kannan, Saravanadevi Sivanesana

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Oxidative stress is known to depreciate normal functioning of osteoblast cells. Present study reports oxidative/inflammatory signatures in fluoride exposed human osteosarcoma (HOS) cells and its possible association with the genes involved in bone developmental pathway. Microarray analysis was performed to understand the possible molecular mechanisms of stress-mediated bone lose in HOS cells. Cells were chronically exposed with sub-lethal concentration of fluoride. Global gene expression is profiling revealed 34 up regulated and 2598 down-regulated genes, which were associated with several biological processes including bone development, osteoblast differentiation, stress response, inflammatory response, apoptosis, regulation of cell proliferation. Microarray data were further validated through qRT-PCR and western blot analyses using key representative genes. Based on these findings, it can be proposed that chronic exposure of fluoride may impair bone development via oxidative and inflammatory stress. The present finding also provides important biological clues, which will be helpful for the development of therapeutic targets against diseases related bone.

Keywords: bone, HOS cells, microarray, stress

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Authors: Liu Xiaohan

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

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

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Authors: Berina Pilipović, Saša Pilipović, Maja Pašić-Kulenović

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Inflammation is the body's response to impaired homeostasis caused by infection, injury or trauma resulting in systemic and local effects. Inflammation causes the body's response to injury and is characterized by a series of events including inflammatory response, response to pain receptors and the recovery process. Inflammation can be acute and chronic. The inflammatory response is described in three different phases. Free radical is an atom or molecule that has the unpaired electron and is therefore generally very reactive chemical species. Biologically important example of reaction with free radicals is called Lipid peroxidation (LP). Lipid peroxidation reactions occur in biological membranes, and if at the outset is not stopped with the action of antioxidants, it will bring damage to the membrane, which results in partial or complete loss of their physiological functions. Calcium antagonists and beta-adrenergic receptor antagonists are known drugs, and for many years and widely used in the treatment of cardiovascular diseases. Some of these compounds also show antioxidant activity. The mechanism of antioxidant activities of calcium antagonists and beta-blockers is unknown, since their structure varies widely. This research investigated the possible local anti-inflammatory activity of ointments containing 1% carvedilol in the white petrolatum USP. Ear inflammation was induced by 3% croton oil acetone solution, in quantity of 10 µl on both mouse ears. Albino Swiss mouse (n = 8) are treated with 2.5 mg/ear ointment, and control group was treated on the same way as previous with hydrocortisone 1% ointment (2.5 mg/ear). The other ear of the same animal was used as control one. Ointments were administered once per day, on the left ear. After treatment, ears were observed for three days. After three days, we measured mass (mg) of 6 mm ear punch of treated and controlled ears. The results of testing anti-inflammatory effects of ointments with carvedilol in the mouse ear model show stronger observed effect than ointment with 1% hydrocortisone in the same basis. Identical results were confirmed by the difference between the mass of 6 mm ears punch. The results were also confirmed by histological examination. Ointments with carvedilol showed significant reduction of the inflammation process caused by croton oil on the mouse inflammation model.

Keywords: antioxidant, carvedilol, inflammation, mouse ear

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Authors: Sadia Arshad, Yifa Tang, Dumitru Baleanu

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A fractional order mathematical model is proposed that incorporate CD8+ cells, natural killer cells, cytokines and tumor cells. The tumor cells growth in the absence of an immune response is modeled by logistic law as it was the simplest form for which predictions also agreed with the experimental data. Natural Killer Cells are our first line of defense. NK cells directly kill tumor cells through several mechanisms, including the release of cytoplasmic granules containing perforin and granzyme, expression of tumor necrosis factor (TNF) family members. The effect of the NK cells on the tumor cell population is expressed with the product term. Rational form is used to describe interaction between CD8+ cells and tumor cells. A number of cytokines are produced by NKs, including tumor necrosis factor TNF, IFN, and interleukin (IL-10). Source term for cytokines is modeled by Michaelis-Menten form to indicate the saturated effects of the immune response. Stability of the equilibrium points is discussed for biologically significant values of bifurcation parameters. We studied the treatment of fractional order system by investigating analytical conditions of tumor eradication. Numerical simulations are presented to illustrate the analytical results.

Keywords: cancer model, fractional calculus, numerical simulations, stability analysis

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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

Procedia PDF Downloads 322

Authors: Chakrit Thapphan, Suteeraporn Chaowattanapanit, Sorutsiri Chareonsudjai, Wisitsak Phoksawat, Supranee Phantanawiboon, Kiatichai Faksri, Steve W. Edwards, Kanin Salao

Abstract:

Background: Psoriasis is a chronic inflammatory disease of the skin that is mediated by crosstalk between keratinocytes and immune cells, especially CD4+ T helper (Th) cells. To date, psoriasis is established as a T helper 17 (Th17) cell-mediated inflammatory process driven by the over-expression of Th17. However, the role of other CD4+T helper cells is rather controversial. Objective: Our study, thereby, aimed to characterize and analyze T cell subsets in the circulating blood of psoriasis patients and compare them to healthy controls. Methods: Peripheral blood mononuclear cells were isolated from the participants and stained with fluorescent dye-conjugated monoclonal antibodies specific for intracellular cytokines, including interferon-gamma (IFN- γ), interleukin (IL-4), IL-17 and forkhead box P3 (FOXP3), that can be used to define T helper 1 (Th1) cells, T helper 2 (Th2), T helper 17 (Th17) and regulatory T cells (Treg) respectively. Results: We found that the numbers of Th2 (59.6% ± 17.0) and Th17 (4.0% ± 2.0) cells in the circulating blood of psoriasis patients were significantly higher than those of the healthy controls (p= 0.0007 and 0.0013 respectively). In contrast, the numbers of Th1 and Treg cells were not significantly different between psoriasis patients and healthy controls (p= 0.0593 and 0.8518, respectively). Additionally, when adjusting these numbers of Th cells to Treg, we observed a similar trend that the ratio of Th2/Treg and Th17/Treg also elevated (p = 0.0007 and 0.0047, respectively). Conclusion: Taken together, our results suggest an imbalanced T exhibit toward the Th2 and Th17 skewed-immune responses in psoriasis patients.

Keywords: psoriasis, Th cell subsets, Th2 cells, Th17 cells, Treg cells

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Authors: Mukta Singh, Ratan Kumar Saha, Himadri Saha, Paramveer Singh

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The present study evaluated the effect of sub-lethal doses of antifungal drug miconazole nitrate (MCZ) on immunological responses including immune-related gene expression and its role as a prophylactic drug against S. parasitica in Labeo rohita fingerlings. Fish were fed with sub lethal doses of MCZ i.e., T1- 6.30 mg MCZ kgBW⁻¹, T2- 12.61 mg MCZ kgBW⁻¹ and T3- 25.22 mg MCZ kgBW⁻¹ and sampling was done at different time intervals for 240 h. Immunological parameters viz. lysozyme activity, oxygen radical production and plasma anti-protease activity showed significant enhancement (p < 0.05) in fish fed with T2 and T3 doses. Significant reduction in plasma protein content was observed in all the dietary groups as compared to control. Expression of immune-relevant genes like TLR-22 and β2-M showed significantly higher expression at six h and 24 h of sampling in both liver and head-kidney. However, these genes showed a down-regulation after 120 h of sampling in both the tissues. Preventive efficacy study showed that single dose of MCZ provides protection against oomycetes up to the fourth day of infection. Significantly higher mortality was observed in control diet-fed fish as compared to fish fed with MCZ medicated diet. Thus, from the study, it can be concluded that the MCZ can act as a potent antifungal agent for preventing oomycetes infection as well as to enhance the immune response.

Keywords: antifungal, immune gene, immunological, miconazole nitrate, prophylactic

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Authors: Wissam Aljundi, Loay Daas, Yaser Abu Dail, Barbara Käsmann-Kellner, Berthold Seitz, Alaa Din Abdin

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Purpose: To investigate the effectiveness of nonsteroidal anti-inflammatory eye drops (NSAIDs) combined with oral acetazolamide for postoperative macular edema (PME) after uncomplicated phacoemulsification (PE) and to identify predictors of non-response. Methods: We analyzed data of uncomplicated PE and identified eyes with PME. First-line therapy included topical NSAIDs combined with oral acetazolamide. In case of non-response, triamcinolone was administered subtenonally. Outcome measures included best-corrected visual acuity (BCVA) and central macular thickness (CMT). Results: 94 eyes out of 9750 uncomplicated PE developed PME, of which 60 eyes were included. Follow-ups occurred 6.4±1.8, 12.5±3.7, and 18.6±6.0 weeks after diagnosis. BCVA and CMT improved significantly in all follow-ups. 40 eyes showed response to first-line therapy at first follow-up (G1). The remaining 20 eyes showed no response and required subtenon triamcinolone (G2), of which 11 eyes showed complete regression at the second follow-up and 4 eyes at the third follow-up. 5 eyes showed no response and required intravitreal injection. Multivariate linear regression model showed that diabetes mellitus (DM) and increased cumulative dissipated energy (CDE) are predictors of non-response. Conclusion: Topical NSAIDs with acetazolamide resulted in complete regression of PME in 67% of all cases. DM and increased CDE might be considered as predictors of nonresponse to this treatment.

Keywords: postoperative macular edema, intravitreal injection, cumulative energy, irvine gass syndrome, pseudophakie

Procedia PDF Downloads 87