6^th International Conference and Expo on Immunology October 24-25, 2016 Chicago,IL, USA

Biography:

Yong Ying has completed her Medicine degree from Shanghai Second Medical University, Shanghai China and was a Physician. She has worked for Children’s Hospital of Los Angeles, University of Southern California, School of Medicine, Abbott Laboratories and currently employed by Genentech as a Senior Scientific Researcher since 9 years.

Abstract:

PK characterization is a key step in the drug development process. In preclinical studies approximately 40% of therapeutic monoclonal antibodies (mAbs) tested in cynomolgus monkeys has atypically fast clearance. There are currently efforts to understand and mitigate the lead selection process to improve translational success in the clinic. One approach has been to investigate how antibody variable fragment (Fv) charge impacts PK and bioavailability of therapeutic antibodies. An empirical model was used to test the role of antibody Fv charge on PK properties by systematic amino acid substitutions in the Fv region of two mAbs, rhuMAbX and rhuMAbY. We compared the PK results of the parental mAbs and Fv charge variants to test our prediction for non-specific clearance. Given the large number of samples and low volumes we selected the Gyros platform for PK assay development and sample analysis. PK assays were developed and qualified successfully for the two parental mAbs and their two variants in three preclinical species (Cynomolgus monkey, Rat and Mouse). We present our results as well as our strategy in utilizing micro-sampling and the Gyros technology as a cost and time effective approach to streamline and improve efficiency for screening and selection of therapeutic mAb lead candidates for clinical development.

Biography:

Jeong-Eun Huh working in the Research Center for Cellular Homeostasis in Ewha Womans University. A major in molecular and cellular bone biology, she has published 3 peer-reviewed paper. Her primary research interests are in the field of osteoimmunology, especially the mechanisms of osteoclastogenesis. She received a research fellowship grant from the National Research Foundation of Korea (NRF). Her long term goal is to target signaling pathways as a novel approach to therapy.

Abstract:

The mitochondrial sirtuin 3 (SIRT3) is involved in suppressing the onset of multiple pathologies, including cardiovascular disease, fatty liver, breast cancer and age-related disorders. However, its role in bone metabolism is not known. Here we show the involvement of SIRT3 in osteoclast differentiation. Receptor activator of nuclear factor-κB ligand (RANKL), an essential cytokine for osteoclastogenesis, induces the expression of both the transcription co-activator peroxisome proliferator-activated receptor-γ co-activator-1β (PGC1β) and the nuclear receptor estrogen receptor-related receptor α (ERRα), which coordinately up-regulated SIRT3 during osteoclast differentiation from bone marrow-derived monocytes/macrophages (BMMs). SIRT3-deficient mice exhibit decreased bone mass compared with wild-type mice due to increased numbers of osteoclasts. Consistently, Sirt3^-/- osteoclast precursor cells underwent increased osteoclastogenesis in response to RANKL, whereas SIRT3 overexpression in osteoclast precursor cells exhibited reduced the formation of osteoclasts. Strikingly, Sirt3^-/- osteoclast precursor cells reduced AMP-activated protein kinase (AMPK) phosphorylation through down-regulating the expression of AMPK that plays a key role in regulating cellular energy metabolism during RANKL-induced osteoclast differentiation. These data demonstrate that a mitochondrial SIRT3 is an intrinsic inhibitor for RANKL-mediated osteoclastogenesis.

Biography:

Hyung-Ran Kim has completed her PhD from Yonsei University and Postdoctoral studies from Ewha Womans University School of Medicine. She is a Research Professor of Department of Microbiology. She has studied regulatory T cells and their own activity for suppression of immune responses.

Abstract:

Reactive oxygen species (ROS) have been considered harmful to tissues and as mediators of inflammation at the injury sites for a long time. However, in recent, many findings about other functions of ROS and oxygen are reported. The effects of ROS such as suppression of autoimmune disease and allergen-induced inflammation have been studied. Moreover, regulatory T cell (Treg) effects to various diseases including autoimmune and inflammatory diseases depending on own activity. There are also many reports on the therapeutic effects of hyperbaric oxygen therapy (HBOT) in chronic inflammatory or autoimmune diseases. We hypothesized that HBOT may improve arthritis symptoms. DBA1/J mice were used for entire experiments. Arthritis was induced by bovine type II collagen. HBOT protocol is 100% O₂ and 3 atm for 90 min after 30 min of compression and then followed by 45 min of decompression daily. We detected paw thickness by macroscopic anatomy and histological score by hematoxylin & eosin staining. Type II collagen antibodies and rheumatoid factors in serum were detected by ELISA. Expressions of some molecules related with Treg and oxygen were detected by immunoblotting. HBOT relieved paw thickness and decreased collagen antibodies and rheumatoid factors in serum. HBOT also reduced inflammation of synovial tissue. HBOT decreased protein expression of p-STAT3 and HIF-1α and increased that of IDO and FoxP3 in paw tissues of murine arthritis model. These data indicate that HBOT attenuated arthritis in DBA1/J mice through activation of Treg and regulation of some molecules related oxygen.

Biography:

Abstract:

RBJ has been identified to be dysregulated in gastrointestinal cancer and promotes tumorigenesis and progression by mediating nuclear accumulation of active MEK1/2 and sustained activation of ERK1/2. Considering that nuclear accumulation and constitutive activation of MEK/ERK not only promotes tumor progression directly but also induces chronic inflammation, we wonder whether and how RBJ impairs host immune-surveillance via chronic inflammation and consequently supports tumor progression. Here, we report that higher expression of RBJ in human breast cancer tissue has been significantly correlated with poorer prognosis in breast cancer patients. The forced expression of RBJ promotes tumor growth and metastasis both in vitro and in vivo. In addition, more accumulation of immune suppressive cells but less anti-tumor immune cell sub-populations were found in spleen and tumor tissue derived from RBJ force-expressed tumor-bearing mice. Furthermore, forced RBJ expression significantly promotes tumor cell production of pro-inflammatory cytokine IL-6 by constitutive activating MEK/ERK signaling pathway. Accordingly, RBJ knockdown significantly decreases tumor growth and metastasis in vitro and in vivo with markedly reduced production of IL-6. Administration of anti-IL-6 neutralizing antibody could reduce MDSCs accumulation in tumor tissue in vivo. Therefore, our results demonstrate that RBJ-mediated nuclear constitutive activation of ERK1/2 leads to persistent production of IL-6 and increase of MDSCs recruitment, contributing to promotion of tumor growth and metastasis. These results suggest that RBJ contributes to tumor immune escape, maybe serving a potential target for design of antitumor drug.

Biography:

Abdulrahman Khazim Al-Asmari is known for his scientific contributions in the field of toxinology. At present he is undertaking research projects to study the natural toxins such as the venoms of scorpion and snakes and their different fractions for treating different diseases including cancer.  He is the author and coauthor of more than 50 publications which were published in reputed international and national journals. He is also the author of several books and book chapters published by International publishers of repute. He is a member of the Editorial Board of many journals of prestigious national and international scientific societies and committees.

Abstract:

Scorpion venoms efficiently block the neurotransmitter signaling pathway by prejudicing the ion channel operating mechanism in the body system. This massive effect of ion channel impairment by the venom is due to the presence of various macromolecules such as proteins and peptides in it. Beside its negative effect, venoms also possess some of the beneficial aspect for the human being. The venom has also been shown to exhibit anti-cancer properties in various cancer types. This unique property of the venom as anti-cancer agent is mainly due to its role in creating apoptosis and also inhibiting several signaling cascade mechanism which promotes cancer cell proliferation and growth. In this study we examine the effect of venom (obtained from our local serpentarium facility) on the phenotypic changes as well as change at the molecular levels in colorectal and breast cancer cell lines. A dramatic decrease in cell invasion was observed in both the cancer cell lines upon venom treatment. We observed 60-90% decrease in this parameter which is an important hallmark of cancer progression. Additionally, a decrease in IL-6 as well as in RhoC expression indicates anti-cancer properties of the venoms used in this study. Additionally, decrease in the phosphorylation of Erk^1/2 and STAT3 gives strong messages of its anti-cancer properties. In addition to this, decrease in the expression of pro-apoptotic proteins such as Bcl2 (Bcl-X_L) and BID and up-regulation of anti-apoptotic/tumor suppressor protein (p⁵³) by the colorectal and breast cancer cell lines when treated with venoms indicates its role as a pro-apoptotic agent. In addition to this, a vivid picture of DNA damage in comet assay was also observed in venom treated cell lines. Our study is in agreement with the previous work showing the anti-cancer property of scorpion venom. In conclusion, the scorpion venom obtained at our research center at Prince Sultan Military Medical City (PSMMC) possesses significant potential to act as an anti-cancer agent against colorectal and breast cancer cell lines.

Biography:

Fanny Chmilewsky has completed her PhD in 2013 from Aix-Marseille University and currently doing postdoctoral research from University of Illinois at Chicago College of Dentistry. She has exemplary training in pulpal biology with expertise in pulp regeneration and complement system research. She has published her research in very reputed journals such as Journal of Dental Research and American Journal of Pathology.

Abstract:

Given the importance of sensory innervation in tooth vitality, the identification of signals that control nerve regeneration and the cellular events they induce is essential to identify new therapeutic targets. The complement anaphylatoxin C5a, which is one of the very first components of innate immunity and inflammation is produced at the injured site of human carious teeth and plays an important role in dental-pulp regeneration via interaction with nearby dental pulp cells­. We extend these observations in dental nerve regeneration research with regard to local production of neurotrophins by pulp fibroblasts upon carious injury. Recently we demonstrated that caries-associated C5a receptors (C5aR) expression is followed by its activation by the C5a generated from the activation of complements molecules expressed by pulp fibroblasts. C5aR signaling results in brain-derived nerve growth factor (BDNF) secretion by pulp fibroblasts that induces prominent neurite outgrowth toward the site of carious injury. Previously another C5a receptor, C5L2, has been identified. Since no signaling pathway is induced following its interaction with C5a, it received very little attention. In this study, our results further demonstrate that newly generated C5aR in human pulp are co-localized with C5L2 both in vivo and in vitro shortly after carious injury. Furthermore, C5L2 siRNA-silencing significantly increased BDNF-secretion in LTA-stimulated pulp fibroblasts. Thus the C5aR and C5L2 studies in the regenerative process could provide innovative therapeutic strategy, i.e., the possibility to enhance and/or prolong the positive action of C5a in dental pulp regeneration by activating or blocking these active and inactive receptors.

Biography:

Bakaeva Zanda Valerievna has completed PhD and postdoctoral studies from Department of Human and Animal Physiology, Faculty of Biology, Lomonosov Moscow State University. She is the senior researcher of Laboratory of Neurobiology, Scientific Center of Children's Health of the Russian Federation Ministry of Health. She has published more than 25 papers in reputed journals. She is the docent at the Department of Physiology People’s Friendship University of Russia.

Abstract:

Cytokines plays an important role in the development and course of diseases of different systems, including the digestive system. Lymphocytes of regional lymph nodes are the main sources of cytokines which are involved in inflammation. We compared systemic and local cytokine profile of rats with acetate ulcer (AU). Blood was collected from the jugular vein of the rats on the day 4 and 7 after acetate-induced ulceration. Max. AU – after 3 days, 10 days formed scar.  ln. gastricus caudalis of rats were used as the source of T-lymphocytes. Cytokine’s levels were determined in the serum and in the supernatant of mitogen-activated mononuclear cells by flow cytometry. The max. concentration of IL-1α and MCP-1 in the serum of rats without ulcers (IR) was 61.9±15.1 pg/ml and 537.2±82.2 pg/ml resp. Other cytokines were <10 pg. The AU formation induced a significant increase of IL-1α and MCP-1 in the serum in 2.2 and 13.5 times. The level of the other cytokines did not change. The max. of IL-1α, MCP-1, IL-17α, IFNg, IL-4, TNFα in the supernatant of lymph node cells were equal to 273.0±24.6, 62.7±8.7, 2852.8±146.5, 1115.9±168.8, 598.9±33.8, 87.5±18.1 pg/m, resp. AU formation was accompanied by an acute shortage of all local cytokines. This continued on the day 7, expressly were low IL-1α and MCP-1, alone IL-17α reverted to normal. So, despite that the development and healing of AU were accompanied by high content in serum of basic proinflammatory cytokines, contrary local immunity is suffer from their deficiency. At help comes IL-17α.

Biography:

Paloma Manea is a Specialist in Cardiology and Internal Medicine, competence in echocardiography and Lecturer at Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania. In 2013, she discovered the 6^th case (there are only 5 communicated cases, worldwide) of spontaneous closure of an interventricular septal defect after a myocardial infarction. She has published and communicated 80 scientific works. Her main research areas are related to angiotensin-renin-aldosterone system, skin cancer, correlations between dentistry and medical diseases and geriatric pathology.

Abstract:

The study monithorized 42 patients with renovascular hypertension, due to renal artery stenosis, followed for 24 months. The patients were divided in 2 groups: Group A with systolic dysfunction and group B without systolic dysfunction. Clinical approach and laboratory parameters (serum creatinine, creatinine clearance, transaminases, serum electrolytes, glycemia, lipid profile, complete blood count, brain natriuretic peptide-BNP, high sensitivity C reactive protein, microalbuminuria, complement C3, electrocardiogram, transthoracic echocardiogram, renal artery sonogram) were performed every 6 months. The statistical analysis revealed a strong correlation between low levels of complement C3 and severe systolic dysfunction (r=0.826 and p=0.02). Previous studies noticed the implication of complement C3 in renal ischemia, especially in animal models but it seems that this C3 fraction is also connected with the severity of systolic dysfunction, in chronic renal ischemia. This observation will open new perspectives for establishing a long term prognosis of renovascular hypertension, complicated by systolic heart failure; also, it will offer us a better understanding of this disease for improving therapeutic strategy.

Biography:

Huiyun Zhang has completed her PhD in Pathophysiology from Shantou University Medical School in 2007 and Postdoctoral studies from the McMaster University in 2014. She is the Director of Pathophysiology Department, Liaoning Medical University, the Associate Director of Allergy and Clinical Immunology Research Centre, the First Affiliated Hospital of Liaoning Medical University and the Associate Director of Translational Medicine Research Institute, Liaoning Medical University. She has published more than 26 papers in reputed journals and has been serving as an Editorial Board Member of repute.

Abstract:

Since accumulated information indicate that there are several distinctive subtypes of regulatory T-cells (Tregs) in man and each of them seems to play different role in controlling immune system, which complicates the involvement of Tregs in allergy. After introduction of the six subsets of Tregs as well as the corresponding characteristics in our published paper, the roles of the individual subsets of these Tregs were studied. And the results showed that Tregs consist of a small proportion of CD4+ T-cells, including 5.3% of CD4+CD25+FOXP3+ T-cells and 0.1% of CD4+CD25+FOXP3 T-cells (Tr1 cells) in HC peripheral blood; IL-10+ Tregs are major population of Tregs (up to 75.2%), whereas IL-10+ TGF-β1+ Tregs (iTregs) only occupy approximately 3% Tregs in peripheral blood; Down-regulation of Tregs in allergy is mainly a consequence of reduced number of IL-10+ Tregs in peripheral blood; Not only allergic conditions, but also eczema showed down-regulation of Tregs; Approximately 55.5% Tregs are CD127 in peripheral blood and this cell population was dramatically enhanced by up to 90% in allergic conditions; CD8+Tregs (CD8+FOXP3+IL-10+) exhibit a small proportion (1.2%) of CD8+ cells in peripheral blood, and they are decreased under allergic conditions; IL-17+Tregs (CD4+CCR6+FOXP3+IL-17+) rarely exist in peripheral blood. Therefore it is proposed that there may be a novel balance between IL-10+ Tregs and CD127-Tregs which suggests that targeting Treg therapy should be focused on these two cell populations.

Biography:

Magdalena Tary-Lehmann is an Adjunct Associate Professor of Case Western Reserve University (CASE), Department of Pathology, Co-Founding Scientist and Chief Scientific Officer for Cellular Technology Limited (CTL). She has published more than 75 papers in peer-reviewed journals. She provides guidance and oversight for technical operations in the CTL contract laboratory, ensuring the ongoing scientific excellence of CTL. Over the past decade, she has worked with clients to develop and validate reference samples and controls for use in regulated immune monitoring assays.

Abstract:

Assessing immunogenicity is a challenge in the biopharmaceutical industry, as an increasing number of new drugs and vaccines aim to elicit a response from the cellular components (e.g., T cells) of the immune system. Measurements of antibodies in bodily fluids (e.g., by ELISA) have provided robust and reproducible results for decades and such assays have been validated for monitoring of B-cell immunity. In contrast, measuring T-cell immunity has proven to be more of a challenge, due to the need to test live cells in functional assays ex vivo. While T cells play a critical role in tumor rejection, reliable measurements of antigen-specific T cell responses ex-vivo remain seemingly problematic as typically, T cells occur in very low frequencies in test samples, such as peripheral blood. Therefore, monitoring antigen-specific T cells and their effector functions is critical for the understanding of diseases and for proper assessments of the efficacies of specific cancer immune therapies. In addition, for an assay to reliably measure T-cell functions, it needs to be warranted that the test conditions are such that the function of T cells in vitro remains unimpaired relative to ex vivo. In theory, several techniques are available, including the use of HLA/peptide tetramers, intra-cellular cytokine staining, ELISA and ELISPOT. In praxis, however, only ELISPOT assays might meet this need, because of the requirement for very high sensitivity to detect the rare antigen specific T cells, the limited number of cells obtainable from patients, the assay’s independence of the HLA genotype of the test subjects, and the ease of performing the assay. Divergent expression profiles of tumor antigens, even within the tumor of a single patient, make it difficult to come up with a general tumor vaccine or to customize immune therapy for an individual patient. Most tumor antigens correspond to normal self-proteins, against which T cell tolerance has been established, either in the thymus or in the immune periphery. However, this negative selection of the auto-antigen- (tumor antigen) specific T cell repertoire is inherently incomplete, being defined by the T cell activation threshold with the density of the nominal antigen and of co-stimulatory molecules exerting synergistic effects. Tumor antigens typically are cryptic auto-antigens and determinant spreading can render cryptic tumor antigens immunogenic, thereby leading to tumor rejection and resulting in protective anti-tumor immunity. Examples of such successful T cell monitoring in tumor models will be presented.

Biography:

Peisong Gao is currently an Associate Professor of Medicine at The Johns Hopkins University School of Medicine in Baltimore, Maryland. He has received his MD degree and Pulmonary Medicine Training in The Fourth Military Medical University, China. From July 1997 to January 1999, he was a Visiting Research Fellow in Oxford University. He subsequently moved to the University of Wales Swansea for his PhD working in Molecular Genetics of Asthma. In 2002 he became a Postdoctoral Fellow in the Division of Allergy & Clinical Immunology at Johns Hopkins. In 2008 he was promoted to Assistant Professor. His research has been greatly recognized by several awards including the 2004 Research Excellence Award, the 2007 Interest Section Award and Outstanding Pediatric Allergy, Asthma and Immunology Award from AAAAI. His studies mainly focus on gene, environment and development of asthma. He has published more than 60 papers in reputed journals.

Abstract:

We proposed the existence of a protective mechanism through which mannose receptor (MRC1/CD206) limits allergic inflammation via allergen clearance and its intronic miRNA511-3p. Mrc1-null (Mrc1^-/-) mice showed significant reduction in cockroach allergen uptake compared with WT mice and consequently Mrc1^-/- mice had greater lung inflammation, IgE levels and cytokine production in a cockroach allergen-induced mouse model compared to WT mice. MiR-511-3p, encoded within the MRC1 gene was shown to be co-regulated with Mrc1. Macrophages from Mrc1^-/- mice showed significantly reduced levels of miR-511-3p and a M1 phenotype whereas over-expression of miR-511-3p rendered macrophages to exhibit a M2 phenotype. Further, delivery of miR-511-3p in mice led to a significant reduction in cockroach allergen-induced inflammation and this effect was confirmed in the bone-marrow chimeric mice receiving hematopoietic stem and progenitor cells (HS/PCs) over expressing miR-511-3p. The serum levels of miR-511-3p were significantly lower in human asthmatics compared to non-asthmatic subjects. Profiling of macrophages with or without miR-511-3p over-expression identified 729 differentially expressed genes, wherein the level of ptgds2, encoding PGD2 synthase and its product, PGD2 was significantly lower, which might contribute to the protective effect of Mrc1 and miR-511-3p. Collectively, these studies suggest that Mrc1 and its intronic miR-511-3p mediate protection against allergen-induced lung inflammation.

Biography:

Hana Zelenkova has been active in Dermatovenerology since 1973. Since 2000 she has been directing her own Private Clinic of Dermatovenereology. She has given more than 650 expert lectures in Slovak Republic as well as abroad and has 420 scientific publications to her credit. She is the Founder and President of the Slovak Society for Aesthetic and Cosmetic Dermatology President of the traditional international DERMAPARTY congress.

Abstract:

Poor healing wounds of varying aetiology and localization have been the centre of attention among specialists due to the constantly growing number of patients suffering from this problem. The therapy must be based on the stage of healing of the wound; however, according to the TIME model it is necessary to prepare the bottom of the poor healing wound considering biofilm, infection and other circumstances. Systemic application of antibiotics has shown no effect in most cases and what has been gaining attention lately are topical antibacterial preparations including iodine, silver, enzymes, etc. Staphylococci appear in the bottom of the defect quite often and complicate the healing process, not to mention MRSA in quite many cases. The presentation includes the results we have obtained in successfully eliminating Staphylococci including MRSA using Staphylococcus phage lysate developed for topical use only. Its role is to disrupt Staphylococcus cells in the place of infection. After the infection is eliminated, the second stage of healing sets on and common conventional preparations are used. This method significantly shortens the time of healing. The presented results have been obtained in a group of 69 patients with venous ulcerations on lower extremities. Attention should be paid to the great effect of the said Staphylococcus phage lysate and successful elimination of MRSA in 9 patients.

Biography:

Qing Jiang is a Professor in Nutrition Science at Purdue.  She has focused on different forms of vitamin E and novel vitamin E metabolite long-chain carboxychromanols with respect to their anti-inflammatory and anticancer activities in cell-based and preclinical studies.  Her lab has developed various analytical methods for quantifying vitamin E metabolites.   Dr. Jiang has 45 publications and obtained three patents.  She is a member of the editorial board of Journal of Nutritional Biochemistry.  She has served as a reviewer in study sections of NIH and USDA.  She is a recipient of E.L.R. Stokstad Award for outstanding fundamental research in nutrition from American Society for Nutrition and University Faculty Scholar Award from Purdue.

Abstract:

Vitamin E forms are substantially metabolized to various carboxychromanols including 13’-carboxychromanols (13’-COOHs) that are found at high levels in feces. However, there is limited knowledge about functions of these metabolites. Here we studied dT-13’-COOH and dTE-13’-COOH, which are metabolites of d-tocopherol and d-tocotrienol, respectively. Both 13’-COOHs are much stronger than tocopherols in inhibition of pro-inflammatory and cancer promoting cyclooxygenase-2 (COX-2) and 5-lipoxygnease (5-LOX) and in induction of apoptosis and autophagy in colon cancer cells. The anti-cancer effects by 13’-COOHs appeared to be partially independent of inhibition of COX-2/5-LOX. Using liquid chromatography tandem mass spectrometry, we found that 13’-COOHs increased intracellular dihydrosphingosin and dihydroceramides after short-time incubation in HCT-116 cells and enhanced ceramides while decreased sphingomyelins during prolonged treatment. Modulation of sphingolipids by 13’-COOHs was observed prior to or coinciding with biochemical manifestation of cell death. Pharmaceutically blocking the increase of these sphingolipids partially counteracted 13’-COOH-induced cell death. Further, 13’-COOH inhibited dihydroceramide desaturase without affecting the protein expression. In agreement with these mechanistic findings, dTE-13’-COOH significantly suppressed the growth and multiplicity of colon tumor in mice. Our study demonstrates that 13’-COOHs have anti-inflammatory and anticancer activities may contribute to in vivo anticancer effect of vitamin E forms and are promising novel cancer prevention agents.

Biography:

Professor Min Fang got her Ph.D from the Institute of Genetics and Developmental Biology, CAS in 2003. She did her postdoc training in Fox Chase Cancer Center in USA mainly on studying the pathogenesis of viral infection, as well as the mechanisms by which vaccines afford protection. She joined the Institute of Microbiology, CAS in June, 2012 as a professor supported by “Thousand Young Talents Program” of the China’s government. Her work was published in esteemed journals such as: Immunity, J Exp Med, PNAS, Plos Pathogen, etc, and multiply works were selected and referred by the “Faculty of 1000”.

Abstract:

Influenza A virus (IAV) is a major human pathogen with the potential to become pandemic. IAV contains only eight RNA segments; thus, the virus must fully exploit the host cellular machinery to facilitate its own replication. In an effort to comprehensively characterize the host machinery taken over by IAV in mammalian cells, we generated stable A549 cell lines with over-expression of the viral NS1 protein to investigate potential host factors which might be modulated by NS1 protein. We found that viral NS1 protein directly interacted with cellular Rac1 and facilitates viral replication. Further researches revealed that NS1 can down-regulates the activity of Rac1 via post-translational modifications. Therefore, our results demonstrated that the IAV blocked Rac1-mediated host cell signaling transduction to facilitate its own replication through the NS1 protein. Our findings provide a novel insight into the mechanism of IAV replication and also indicate new avenues for the development of potential therapeutic targets.

Biography:

Abstract:

Introduction & Aims: HPV testing is used as a means of triaging cervical smears with low grade squamous abnormalities or as part of co-testing with cytology. While HPV testing has a high sensitivity, it has a low specificity in detecting cervical intraepithelial neoplasia grade 2 and above (CIN 2+) leading to unnecessary colposcopy referrals. We investigate the accuracy of the p16/Ki-67 dual immunocytochemical stain in determining the presence of CIN 2+ lesions and its potential as a superior biomarker for triage.

Materials & Methods: 97 cases of liquid based cervical smears with squamous abnormalities and corresponding histology were collected. The smears were then subjected to the dual stain and HPV testing. The sensitivity and specificity of cytology, dual stain and HPV testing were then calculated using CIN 2+ on histology as a reference standard.

Results: The sensitivity and specificity of the dual stain was 93.7% and 76.5%, cytology was 77.8% and 88.2% while HPV testing was 85.7% and 14.7%. The use of dual stain was estimated to reduce the number of unnecessary colposcopy referrals by significant numbers in women with ASCUS and LSIL if it were used as a triage marker compared to HPV and cytology co-testing.

Conclusion: The P16/Ki-67 dual stain is more specific than HPV testing when triaging low grade and atypical cytology specimens and may help to reduce the number of unnecessary colposcopy referrals. More studies should be performed to further evaluate its role in cervical cancer screening programs.

Biography:

Ahmed G Hegazi is currently a Professor of Microbiology and Immunology in the National Research Center, Egypt. He has received his Master’s degree in 1979 and his PhD in 1981. He has been the Principal Investigator on multiple research projects within the National Research Center. He has published 211 scientific papers and articles in national and international journals. He has served on the board of multiple national and international scientific journals. He is also the President of the Egyptian Environmental Society for Uses and Production of Bee Products, Secretary of the Egyptian Society of Apitherapy, Secretary General of the African Federation of Apiculture Associations and a Member of the International Apitherapy Commission (APIMONDIA). He has received several awards which include First Class Decoration of Excellence (1995), The Senior Scientist Prize of National Research Center, (1996), The National Scientific Prize In Biological Sciences (1990), The Scientific Prize of The National Research Center (1989), 2 Bronze Medals from The International Innovation Fair of the Middle East, Kuwait (2007), awarded Ghazi Wad Allah Salon Prize (2008) and has 4 patents to his credit.

Abstract:

Background: Several therapeutic modalities have been used for treatment of psoriasis. Apitherapy entails the medical use of bee products as honey, bee venom and propolis.

Objectives: To evaluate bee venom honey and propolis, as a new therapeutic modality for localized plaque psoriasis.

Materials & Methods: Eighty patients were randomized into four treatment groups: Group-I: Received intradermal bee venom twice weekly, Group-II: Received topical propolis and honey ointment in Vaseline base, Group-III: Received oral propolis capsules 3 gm/day and group-IV: Received intradermal bee venom, oral and topical honey and propolis, Group-V: Received drugs. Response to treatment was assessed by calculating PASI score and measuring serum interleukins: IFN-γ, interleukin (IL) 1β, IL-4, IL-6, IL-10, tumor necrosis factor alpha (TNFα) was detected before and after 3 months of treatment.

Results: A significant reduction in both PASI score and serum level of IL-1β and IL 6 was observed in all groups. Changes in PASI score, IFN-γ, interleukin (IL) 1β, IL-4, IL-6, IL-10, tumor necrosis factor alpha (TNFα) were significantly reduced in groups I, IV and V compared to groups II and III. All treatments were tolerable with minimal adverse effects.

Conclusions: Intradermal bee venom and oral propolis are safe and effective treatments of localized plaque psoriasis with minimal tolerable side effects intradermal bee venom has superior results than oral or topical honey with propolis when used alone or in combination with propolis.

Biography:

Abstract:

This study was conducted to investigate the influence of propolis on immunological responses with special reference to cytokine level of infected with Toxoplasma gundi and treated with and then the inoculation with 0.1 ml propolis everyday till the end of the experiment (28 days). Immune response of rats was evaluated weekly. Cytokines were detected. The results revealed that the growth promoting effect propolis extract. It was clear that the propolis treated group showed the highest lymphoid organ weight all over the experimental period. Propolis was the highest in the Toxoplasma antibodies titer when comparing with control group from the 2^nd week to the end of experiment. Serum levels of cytokines were consistently higher in the treated and propolis infected rats compared with controls. Serum levels of IFN-γ, IL-1 and IL-6, were elevated only at day 7 post-infection.

Biography:

Mahmoud El Feel is currently working as an Assistant Researcher, Beekeeping Department, Plant Protection Research Institute, Agriculture Research Center, Ministry of Agriculture, Egypt. He has completed his Philosophy of Doctorate and Master of Sciences in Agriculture, Apiculture, Entomology (Plant Protection) from Cairo University, higher study Diploma in Agriculture (Apiculture & Silk culture) from El Menofea University in 2001 and Bachelor of Science in Agriculture, General Plant Production from Alexandria University in 1998.

Abstract:

The objective of this review was to determine the influence of bee venom (BV) as immunostimulant activity and the immunomodulatory activity of BV on cytokines production. Bee venom acts upon both innate and adaptive immune response. Compounds in bee venom decrease proinflammatory cytokine synthesis (IL-2, IL-12 and IL-4), inactivate both the classical and alternative complement pathway and decrease superoxide anion production in neutrophils. It could be concluded that time and dose-dependent response as well as the type of treated cell line could determine the immunosuppressive and/or immunostimulant property of bee venom that could be effective in future therapeutic strategies.

Biography:

Abstract:

This study conducted to investigate the immunological responses of rats infected with Toxoplasma gundi and treated with 15% Capparis spinosa honey (Saudi Arabia) supplemented orally for a period of 35 days. Immune response of rats was evaluated weekly. Cytokines were detected in honey supplement either in non-infected or infected. Mortality and morbidity rate were assayed where the lymphoid organs weight were determined. The results revealed that oral administration of honey as a natural feed additive through the experiment reduced mortality rates, increase in body weight, lymphoid organ weight. Also antibody titer was raised. Serum levels of cytokines were consistently higher in the infected and honey supplemented rats compared with controls. Serum levels of IFN-γ, IL-1 and IL-6 were elevated only at day 14 post- infection.

Biography:

Mona Mostafa Farid Ganem has completed her MB BCh in 2003 from Faculty of Medicine, Cairo University, Master’s degree in Neuropsychiatry from Cairo University in 2009 and Doctorate degree in Neurology also from Cairo University in 2015. She has worked as a Resident in Neurology Departments of Kasr El Eini Hospitals from 2005-2006, new Kaser Al Ainy Hospital Cairo University from 2007-2009, Dar AL Fouad Hospital from 2008-2012. She was an Assistant Researcher of Neurology from 2009-2015 and Researcher of Neurology at National Research Center since 2015, Neurology Consultant at Mostafa Mahmoud Hospital and Outpatient Clinic since 2012 to till date and was also a Neurology Consultant at Asseer Central Hospital Saudi Arabia in 2015 & 2016.

Abstract:

Parkinson's disease (PD) is a neurodegenerative and neuro-inflammatory disorder of the central nervous system, it has been known as movement disorder, also it is becoming recognized that for its non-motor characteristics that includes cognitive difficulties. Cognitive function is broadly defined as an intellectual pro­cess by which one becomes aware, perceives or compre­hends ideas. It involves all aspects of perception, thinking, rea­soning and remembering. Cognitive impairment means a deterioration of the mental processes such as memory, decision, understanding and reasoning. Cognitive impairment may be associated with behavioral disorders. There are different cognitive domains that accompany Parkinson's disease, the most common affected domains include: Executive functions, attention, learning and memory. Many studies reported that Bee venom therapy has anti-inflammatory and anti-neurodegenerative effects that improve PD symptoms. Also it attenuates the activation of the microglial response, reduces expression of the inflammation markers and reducing glutamatergic cell toxicity. Also it was reported that Bee venom therapy plays an important role in improving cognitive functions through blocking small conductance calcium-activated potassium channels (SK channels), also can increase brain-derived neurotrophic factor (BDNF).

Biography:

Qing Jiang, Purdue University, USA

Abstract:

Vitamin E forms are substantially metabolized to various carboxychromanols including 13’-carboxychromanols (13’-COOHs) that are found at high levels in feces. However, there is limited knowledge about functions of these metabolites. Here we studied T-13’-COOH and TE-13’-COOH, which are metabolites of -tocopherol and -tocotrienol, respectively. Both 13’-COOHs are much stronger than tocopherols in inhibition of pro-inflammatory and cancer promoting cyclooxygenase-2 (COX-2) and 5-lipoxygnease (5-LOX), and in induction of apoptosis and autophagy in colon cancer cells. The anti-cancer effects by 13’-COOHs appeared to be partially independent of inhibition of COX-2/5-LOX. Using liquid chromatography tandem mass spectrometry, we found that 13’-COOHs increased intracellular dihydrosphingosin and dihydroceramides after short-time incubation in HCT-116 cells, and enhanced ceramides while decreased sphingomyelins during prolonged treatment. Modulation of sphingolipids by 13’-COOHs was observed prior to or coinciding with biochemical manifestation of cell death. Pharmaceutically blocking the increase of these sphingolipids partially counteracted 13’-COOH-induced cell death. Further, 13’-COOH inhibited dihydroceramide desaturase without affecting the protein expression. In agreement with these mechanistic findings, TE-13’-COOH significantly suppressed the growth and multiplicity of colon tumor in mice. Our study demonstrates that 13’-COOHs have anti-inflammatory and anticancer activities, may contribute to in vivo anticancer effect of vitamin E forms and are promising novel cancer prevention agents.

Biography:

Paloma Manea MD, Ph D, FACCP is a specialist in Cardiology and Internal Medicine, competence in echocardiography, lecturer at ’’Grigore T.Popa’’ University of Medicine and Pharmacy, Iasi, Romania. In 2013, she discovered the 6th case (there are only 5 communicated cases, worldwide) of spontaneous closure of an interventricular septal defect after a myocardial infarction. She has published and communicated 80 scientific works. The main research areas are related to angiotensin-renin-aldosterone system, skin cancer, correlations between dentistry and medical diseases, geriatric pathology.

Abstract:

The study monithorized 42 patients with renovascular hypertension, due to renal artery stenosis, followed for 24 months. The patients were divided in 2 groups: group A, with systolic dysfunction and group B, without systolic dysfunction. Clinical aproach and  laboratory parameters(serum creatinine, creatinine clearance, transaminasis, serum electrolytes,glycemia, lipid profile, complete blood count ,brain natriuretic peptide-BNP, high sensitivity C reactive protein, microalbuminuria, complement C3, electrocardiogram , transthoracic echocardiogram, renal artery sonogram) were performed every 6 months. The statistical analysis revealed  a strong correlation between low levels of complement C3 and severe systolic dysfunction: r = 0.826 and p = 0.02. Previous studies noticed the implication of complement C3 in renal ischemia, especiallly in animal models, but it seems that  this  C3 fraction is also connected with the sesverity of systolic dysfunction, in chronic renal ischemia.. This observation will open new perspectives for establishing a long term prognosis of renovascular hypertension, complicated by systolic heart failure; also, it will offer us a better understanding of this disease , for improving therapeutic strategy.

Biography:

The author (researcher) of the current report, Dr Simon Raymond MPH, is a consultant (specialising in medical and scientific research) and an Alumni of Melbourne University (Rank of Number 1 Australia and Number 33 in the World). The above stated researcher has acted as a reviewer for the respected medical journals and has acted as the principle researcher in the highest powered form of medical trial—Randomised Controlled Trial (RCT).

Abstract:

With respect to viral infections, a situation analysis is performed with identification of significant issues: A) The lack of successful antiviral drugs (therapies) despite many years of pursuit; B) No cure for HIV despite many years of exploration. The pathways to combat HIV and other viruses to date were analysed and the only two significant pathways identified: 1) virus replication; 2) enhancement of immune function. Given the lack of success by these two pathways, it would seem reasonable to direct focus at development of a new strategic pathway. This report presents the development of the new strategic pathway for antiviral therapies represented by “site attachment inhibition (or, negation of cellular attachment by viruses).” Further to this, HIV is used in case analysis with strategic measures detailed including prenatal genetic therapy focusing on mutagenesis and knock out, targeted at genes (receptors; and, surface proteins) including CCR5 and CXCR4, as a means of achieving innate resistance similar to the commonly known CCR5-Δ32 mutation, in addition to treatment strategy following established infection designed to block attachment of the virus to CCR5 and CXCR4, including blockade of the receptors (analogous to beta blockade), stem cell therapy, radiation, and targeted therapy designed to attack the mechanisms of the virus in its attachment ability to the given receptors (CCR5, CXCR4) and any other relevant. Support for site attachment strategy was further consolidated through consideration with respect to advanced information technology in which one key mechanism for virus removal is represented by negation of site attachment. Other strategies and the concept of low-level virus consciousness are presented, in addition to reinforcing new understanding contributed to current medical knowledge.

In conclusion, this report presents the development of the new strategic pathway for antiviral therapies represented by site attachment inhibition (or, negation of cellular attachment by viruses).

Biography:

HuiyunZhang has completed his PhD in Pathophysiology from Shantou University Medical School in 2007 and postdoctoral studies from the McMaster University in 2014. She is the director of Pathophysiology Department, Liaoning Medical University, the associate director of Allergy and Clinical Immunology Research Centre, the First Affiliated Hospital of Liaoning Medical University, and the associate director of of  Translational Medicine Research Institute, Liaoning Medical University. Published more than 26 papers in reputed journals and has been serving as an editorial board member of repute.

Abstract:

Since accumulated information indicate that there are several distinctive subtypes of regulatory T cell s (Tregs) in man, and each of them seems to play different role in controlling immune system, which complicates the involvement of Tregs in allergy. After introduction of the six subsets of Tregs as well as the corresponding characteristics in our published paper, the role of the individual subsets of these Tregs were studied. And the results showed that Tregs consist of a small proportion of CD4+ T cells, including 5.3% of CD4+CD25+FOXP3+ T cells and 0.1% of CD4+CD25+FOXP3- T cells (Tr1 cells) in HC peripheral blood; IL-10+ Tregs  are major population of Tregs (up to 75.2%), whereas IL-10+ TGF-β1+ Tregs (iTregs) only occupy approximately 3% Tregs in peripheral blood; Down-regulation of Tregs in allergy is mainly a consequence of reduced number of IL-10+ Tregs in peripheral blood; Not only allergic conditions, but also eczema showed down-regulation of Tregs; Approximately 55.5% Tregs are CD127- in peripheral blood, and this cell population was dramatically enhanced by up to 90%  in allergic conditions; CD8+Tregs (CD8+FOXP3+IL-10+) exhibit a small proportion (1.2%) of CD8+ cells in peripheral blood, and they are decreased under allergic conditions; IL-17+Tregs (CD4+CCR6+FOXP3+IL-17+) rarely exist in peripheral blood. Therefore it is proposed that there may be a novel balance between IL-10+ Tregs and CD127-Tregs which suggests that targeting Treg therapy should be focused on these two cell populations.

Biography:

Qiuyan Liu, Second Military Medical University, China

Abstract:

RBJ has been identified to be dysregulated in gastrointestinal cancer and promotes tumorigenesis and progression by mediating nuclear accumulation of active MEK1/2 and sustained activation of ERK1/2. Considering that nuclear accumulation and constitutive activation of MEK/ERK not only promotes tumor progression directly but also induces chronic inflammation, we wonder whether and how RBJ impairs host immune-surveillance via chronic inflammation and consequently supports tumor progression. Here, we report that higher expression of RBJ in human breast cancer tissue has been significantly correlated with poorer prognosis in breast cancer patients. The forced expression of RBJ promotes tumor growth and metastasis both in vitro and in vivo. In addition, more accumulation of immune suppressive cells but less anti-tumor immune cell subpopulations were found in spleen and tumor tissue derived from RBJ force-expressed tumor-bearing mice. Furthermore, forced RBJ expression significantly promotes tumor cell production of pro-inflammatory cytokine IL-6 by constitutive activating MEK/ERK signaling pathway. Accordingly, RBJ knockdown significantly decreases tumor growth and metastasis in vitro and in vivo, with markedly reduced production of IL-6. Administration of anti-IL-6 neutralizing antibody could reduce MDSCs accumulation in tumor tissue in vivo. Therefore, our results demonstrate that RBJ-mediated nuclear constitutive activation of ERK1/2 leads to persistent production of IL-6 and increase of MDSCs recruitment, contributing to promotion of tumor growth and metastasis. This results suggest that RBJ contributes to tumor immune escape, maybe serving a potential target for design of antitumor drug.
 

Biography:

Sangeeta Mantoo, Singapore General Hospital, Singapore

Abstract:

Introduction & Aims
HPV testing is used as a means of triaging cervical smears with low grade squamous abnormalities or as part of co-testing with cytology. While HPV testing has a high sensitivity, it has a low specificity in detecting cervical intraepithelial neoplasia grade 2 and above (CIN 2+) leading to unnecessary colposcopy referrals. We investigate the accuracy of the p16/Ki-67 dual immunocytochemical stain in determining the presence of CIN 2+ lesions and its potential as a superior biomarker for triage.

Materials and Methods
97 cases of liquid based cervical smears with squamous abnormalities and corresponding histology were collected. The smears were then subjected to the dual stain and HPV testing. The sensitivity and specificity of cytology, dual stain and HPV testing were then calculated using CIN 2+ on histology as a reference standard.

Results
The sensitivity and specificity of the dual stain was 93.7% and 76.5%, cytology was 77.8% and 88.2% while HPV testing was 85.7% and 14.7%. The use of dual stain was estimated to reduce the number of unnecessary colposcopy referrals by significant numbers in women with ASCUS and LSIL if it were used as a triage marker compared to HPV and cytology co-testing

Conclusion
The P16/Ki-67 dual stain is more specific than HPV testing when triaging low grade and atypical cytology specimens and may help to reduce the number of unnecessary colposcopy referrals. . More studies should be performed to further evaluate its role in cervical cancer screening programmes.

Biography:

M. Tary-Lehmann is an Adjunct Associate Professor of Case Western Reserve University (CASE) Department of Pathology, Co-Founding Scientist and Chief Scientific Officer for Cellular Technology Limited (CTL).  She has published more than 75 papers in peer-reviewed journals.  She provides guidance and oversight for technical operations in the CTL contract laboratory, ensuring the ongoing scientific excellence of CTL.  Over the past decade, she has worked with clients to develop and validate reference samples and controls for use in regulated immune monitoring assays.

Abstract:

Assessing immunogenicity is a challenge in the biopharmaceutical industry, asan increasing number of new drugs and vaccines aim to elicit a response from the cellular components (e.g. T cells) of the immune system.  Measurements of antibodies in bodily fluids (e.g., by ELISA) have provided robust and reproducible results for decades, and such assays have been validated for monitoring of B-cell immunity.  In contrast, measuring T-cell immunity has proven to be more of a challenge, due to the need to test live cells in functional assays ex vivo.  While T cells play a critical role in tumor rejection, reliable measurements of antigen-specific T cell responses ex-vivo remain seemingly problematic, as typically, T cells occur in very low frequencies in test samples, such as peripheral blood.  Therefore, monitoring antigen-specific T cells and their effector functions is critical for the understanding of diseases, and for proper assessments of the efficacies of specific cancer immune therapies.  In addition, for an assay to reliably measure T-cell function(s), it needs to be warranted that the test conditions are such that the function of T cells in vitro remains unimpaired relative to ex vivo.  In theory, several techniques are available, including the use of HLA/peptide tetramers, intra-cellular cytokine staining, ELISA and ELISPOT.  In praxis, however, only ELISPOT assays might meet this need, because of the requirement for: (i) very high sensitivity to detect the rare antigen specific T cells, (ii) the limited number of cells obtainable from patients, (iii) the assay’s independence of the HLA genotype of the test subjects, and (iv) the ease of performing the assay.

Divergent expression profiles of tumor antigens, even within the tumor of a single patient, make it difficult to come up with a general tumor vaccine, or to customize immune therapy for an individual patient.  Most tumor antigens correspond to normal self-proteins,against which T cell tolerance has been established, either in the thymus or in the immune periphery.  However, this negative selection of the auto-antigen- (tumor antigen-) specific T cell repertoire is inherently incomplete, being defined by the T cell activation threshold, with the density of the nominal antigen and of co-stimulatory molecules exerting synergistic effects.  Tumor antigens typically are cryptic auto-antigens, and determinant spreading can render cryptic tumor antigens immunogenic, thereby leading to tumor rejection, and resulting in protective anti-tumor immunity.  Examples of such successful T cell monitoring in tumor models will be presented.

Biography:

Ambreen Gul Muazzam obtained the Certificate in Life Science Enterprise (LSE) from University of Toronto, School of Continuing studies, Mississauga campus, Ontario, Canada. She joined the Institute of Biomedical and Genetic Engineering (IB&GE) in 2003 as scientific officer after receiving her Master’s degree in Biochemistry and Molecular Biology from Quaid-i-Azam University, Islamabad, Pakistan. Then she was promoted to the post of senior scientist in the year 2008. Concurrently, she has completed her M.Phil from Quaid-i-Azam University, Islamabad, Pakistan. She has published papers in international journals. Her research interests include population and disease genetics. Her particular research focus is on diagnostics and molecular studies of Hepatitis B and C as it is one of the major health problems that Pakistan is facing. She is also involved in cell culturing and cytotoxicity of nanoparticles and organic compounds against human cancerous cell lines. She has also experience working in the quality control department of pharmaceutical company as a microbiologist

Abstract:

Introduction

Rheumatoid arthritis is an autoimmune disease with poorly understood pathophysiology. Genetic components of disease etiology, especially human leukocyte antigen (HLA) associations, are well known. Ethnic differences account for a number of variations in disease association with the HLA locus and there seem to be differences in various studies regarding its genetic predisposition. This study was aimed at determining the contribution of DRB1 and DQB1 components of HLA class II in rheumatoid arthritis in a Pakistani cohort.

Method

For this study, 110 patients and 120 healthy controls from the same geographical area and matched ethnicity were enrolled. Blood DNA was isolated from all the subjects and HLA alleles were typed following allele specific amplification. Subsequently, haplotypes were generated and allelic and haplotype distribution frequencies were compared among the patients and controls using χ² and Arlequin software. The data obtained by this analysis were also compared with other reported associations found in the Pakistani population by meta-analysis.

Results

HLA allelic status was determined among the patients and controls from the same geographical area to account for differences in ethnicity and environmental factors. Significant associations were found for alleles as well as haplotypes among the patients of rheumatoid arthritis. DRB1*10, DQB1*05 and DQB1*602 were found to be associated with disease susceptibility, whereas DRB1*11 and DQB1*02 had protective effect against the disease. Similarly, haplotype DRB1*10-DQB1*05 was associated disease risk, whereas DRB1*07-DQB1*02 and DRB1*11-DQB1*0301 had a protective effect.

Conclusion

There is a significant DRB1and DQB1 allele and haplotype association with rheumatoid arthritis susceptibility and protection.

Biography:

Abstract:

Influenza A virus (IAV) is a major human pathogen with the potential to become pandemic. IAV contains only eight RNA segments, thus, the virus must fully exploit the host cellular machinery to facilitate its own replication. In an effort to comprehensively characterize the host machinery taken over by IAV in mammalian cells, we generated stable A549 cell lines with over-expression of the viral NS1 protein to investigate potential host factors which might be modulated by NS1 protein. We found that viral NS1 protein directly interacted with cellular Rac1 and facilitates viral replication. Further researches revealed that NS1 can down-regulates the activity of Rac1 via post-translational modifications. Therefore, our results demonstrated that the IAV blocked Rac1-mediated host cell signaling transduction to facilitate its own replication through the NS1 protein. Our findings provide a novel insight into the mechanism of IAV replication and also indicate new avenues for the development of potential therapeutic targets.

Biography:

Sidra Islam is pursuing her Ph.D from the department of Biochemistry, Faculty of Medicine, Aligarh Muslim University, Aligarh. She has published 3 papers in international journals and 2 are in communication. She has qualified NET-LS and GATE.

Abstract:

Immunoglobulin G (IgG) is the most abundant immunoglobulin of the total immunoglobulin pool in the serum and has been found susceptible to damage by reactive oxygen species (ROS). This study aims at exploring the alterations in the structural characteristics using various biophysical and biochemical methods. Modified IgG showed hyperchromicity in UV-vis spectroscopy, quenching in tyrosine fluorescence and cross linking in SDS PAGE. Changes in secondary structure were evident by Far UV-CD and FTIR. The modified IgG showed enhanced hydrophobicity, increase in carbonyl and reduction in the sulphydryl content. DLS studies point towards increase in the hydrodynamic radii, while DSC analysis showed enhanced thermodynamic stability of the modified IgG. Hydroxyl radical induced aggregation was confirmed by enhanced ThT specific fluorescence intensity and a red shift in the Congo red specific fluorescence intensity in the modified IgG and by the transmission electron microscopy. The immunogenic potential of native and OH^• treated IgG was probed in experimental animal. The modified IgG was highly immunogenic inducing high titer antibodies. Furthermore, antibodies against native and OH^•  modified IgG in RA patients were detected by direct binding and inhibition ELISA. The data showed preferential binding of RA autoantibodies to hydroxylated IgG in comparison to the native counterpart. Thus it can be concluded that structural changes generated neoepitopes on IgG causing enhanced antibody production. Also, OH^• modified IgG can serve as a novel antigen with a possible role in etiopathogenesis of RA.

Biography:

Firoozabadi currently serves as a Professor of Biomedical Engineering and Head of BioMedical Informatics department at Tarbiat Modares University. He has published over 321 papers in peer reviewed journals and international conferences.

He was Research Deputy Dean of Medical Sciences Faculty from 2009-2011, Manager of Apllied Research office (1997-2005) and Head of Medical Physics Department (2008-2010) at Tarbiat Modares University.

 His research and teaching interests include theory and application of bio-electromagnetics, Human-Machine Interaction, bioelectric phenomena and electrophysiology, bio-instrumentation, and biological signal processing.

He is concurrently working in three branches: 1.use of Electromagnetic fields/energy for treatment of cancer, 2. Use of Bio-Electromagnetic fields/energy for empowering the mind (the Passive-Neuro-feedback Systems) and 3. Development of the affective Human-Machine interfaces.

Abstract:

Statement of the Problem:  Electrochemotherapy as a powerful treatment of solid tumors, using electric pulse permeabilize the cells to chemotherapy drug reversibly and in addition to destruction of primary tumor, it is capable of triggering immune antitumor responses and of thus facilitating deletion of tumor cells at metastatic tumor sites. However, the efficacy of such a treatment could be influenced by Confounders like mobile phones waves through phenomena such as adaptive response resulted in decreasing of genotoxic agents effects. This study examines alteration in the antitumor effectiveness of electrochemotherapy treatment when tumor cells were pre-exposed to 900 MHz modulated by 217Hz or 217 Hz fields similar to those generated by mobile phones.

Methodology : The 4T-1 cells were exposed to ELF magnetic fields at 93,120 or 159 mT intensities generated by Helmholtz coils or the radiofrequency (RF) signals modulated by rectangular pulses with a repetition frequency of 217 Hz  (pulse width 0.576 ms) at 17, 162 or 349 mW/cm² power densities generated by GSM900 simulator. Then, the cells were treated by different protocols of electrochemotherapy. After 24h, the cell viability were evaluated by MTT assay.

Findings: The data indicated that although it was not observed any alteration in cell viability as a result of ELF magnetic fields or RF radiations exposure alone, exposure of cells to ELF fields at some flux density before electrochemotherapy to different protocols increases cell viability and thus decrease treatment efficacy. Also, the similar results to that of ELF magnetic fields on treatment efficacy were observed for modulated radiofrequency signals (Figure 1).

Conclusion & Significance: Based on the results of this in vitro study, fields emitted by mobile phones can develop an adaptive response for some electrochemotherapy protocols. Therefore, these results should be extended to in vivo studies and be investigated the other mechanism of electrochemotherapy like stimulation of immune response influenced by mobile phone radiations.

Figure 1: percentage of viable cells for treatment by electrochemotherapy alone and treatments (three protocol of electrochemotherapy ((70V/cm, 5 kHz), (60 V/cm, 5 kHz), (70 V/cm, 4 kHz) after exposure to (A): ELF magnetic fields 93, 120 or 159 mT (B): RF radiation modulated by 217 Hz 17,162, 349 mW/cm²

Biography:

Anum Liaquat Ali, Dow University of Health Sciences, Pakistan

Abstract:

Background: Latent tuberculosis infection is aymptomatic and untransmissable diseases. According to the World Health Organization (WHO) Global Surveillance and Monitoring Project, in 2014 estimated incidence of TB is 181 per 100 000, with 40% of the population infected with TB in Pakistan and approximately one-third of the population is infected worldwide. Laboratory workers dealing with tan samples or TB patients are always at risk to get TB. In this study we have investigated prevalence of latent TB in health care providers who are at risk to get TB to the cases of infectious tuberculosis using QuantiFERON assay.
Objective: To screen the lab workers at risk to occupational exposure for latent TB using QuantiFERON Assay 
Methodology: 3ml of whole blood were collected into three specific QFT tubes.(NIL,TB, Mitogen) from 60 lab personals including phlebotomists, Medical technologist, doctors and faculty members working closely with TB samples or patients. Samples were performed for detection interferon specifically released against TB according to the manufacturer QuantiFERON TB Gold protocol. 
Result: Out of 60 samples 12 samples were found positive, 1 sample showed indeterminate result and 47 were found negative. Out of 12 positive samples 10 were from medical technologists working closely since long time with TB samples or TB patients and 2 were from phlebotomists collecting samples from patients.
Conclusion:
Health care providers usually work with TB infected samples with minimal infection control measures. This study shows the need for effective latent TB infection control measures and emphasizes on the importance to improve over all biosafety precautions during dealing with the TB patients or samples. The study also provides recommendations for routine and regular screening and checkup of the lab workers working with TB to ensure their safety rather safety of all as no one is safe until everyone is safe.

Biography:

Hisham  AbdEl Dayem, Ain Shams  University Faculty of Medicine, Egypt

Abstract:

Biography:

Abdul Rouf Mir has PhD in Biochemistry from Jawaharlal Nehru Medical College, Faculty of Medicine, Aligarh Muslim University, India. He is currently teaching molecular biology and immunology at Govt. College Baramulla, University of Kashmir, India. His work on Histone glycoxidation and Cancer biology has been in peer reviewed international journals viz, Glycobiology (Oxford Journal), PloS ONE, CCA, IJBM, and others. He is a young researcher and is awaiting a Post Doc position.

Abstract:

The emerging correlation of AGE-RAGE axis with cancers has led researchers to study the role of sugars and their by-products as potential relevant mediators. Where, some workers have established the association between hypergycemia and cancer by investigating AGEs in blood circulation, our group has observed a strong autoimmune response against neo-epitopes generated upon histone proteins due to glycoxidation induced structural perturbations. In this study, we report the methylglyoxal induced conformational changes in histone H1 and H2A leading to modifications in the aromatic residues, changed tyrosine microenvironment, intermolecular cross linking and generation of AGEs, masking of hydrophobic patches and a hypsochromic shift in the in ANS specific fluorescence, amorphous aggregation, thermal stability and the formation of Nε-(carboxyethyl)lysine. Modified histones induced high titre antibodies in rabbits and the IgG isolated form sera of rabbits immunized with modified histones exhibited specific binding with their immunogens in Western Blot analysis. IgG isolated from the sera of patients with different types of cancers  showed better recognition for neo-epitopes on the modified histones in ELISA and gel retardation assay, reflecting the presence of circulating autoantibodies in cancer against glycoxidatively modified histones in cancer patients. Keeping in view the role of protein post translational modifications in stimulating cellular and humoral immune responses, methylglyoxal modified histones may also be considered as potential antigenic candidates for eliciting autoimmune response in cancer patients.

Biography:

Abstract:

Thyroid cancer is the most frequently occurring endocrine cancer. Anaplastic thyroid cancer (ATC) shows very poor prognosis (mean survival < 6 months) and have limited treatment options. TNF-related apoptosis-inducing ligand (TRAIL) can induce tumor cell specific apoptosis in multiple cancers without affecting non-tumor cells.  We have previously demonstrated that Map kinase Activating Death Domain containing protein (MADD), is a cancer cell survival factor, its knockdown leads to cancer cell apoptosis, and Akt-mediated MADD phosphorylation confers resistance to TRAIL induced apoptosis in thyroid cancer. Therefore, we hypothesized that ATC TRAIL sensitivity could be enhanced by preventing MADD phosphorylation. MADD expression and TRAIL resistance was determined by Western blotting and active caspase 3 staining in several ATC cell lines harboring mutations in cancer driver genes including BRAF, Akt, and PTEN. MADD phosphorylation was inhibited by site directed mutagenesis of Akt phosphorylation sites and exogenously expressing the mutant constructs to determine the effect on TRAIL induced apoptosis. MADD was overexpressed in all ATC cells compared to the normal thyroid tissues irrespective of the underlying genetic mutation and/or inherent TRAIL resistance. Further, preventing MADD phosphorylation by site directed mutagenesis in ATC lines resulted in significantly increased TRAIL-induced apoptosis accompanied by the activation of both intrinsic and extrinsic apoptotic pathways. Additionally, we inhibited endogenous MADD phosphorylation by using AKT inhibitors. PI3-kinase inhibitor, which acts upstream of AKT and MADD, in combination with TRAIL showed increased apoptosis in ATC cell lines in comparison to TRAIL or PI3K inhibitor alone. Thus, we conclude that prevention of MADD phosphorylation by site directed mutagenesis or PI3K inhibitors improves TRAIL susceptibility of ATC cells. Further studies are warranted to delineate the underlying mechanism of action, and determine the clinical utility of this approach to treat ATC

Biography:

Abstract:

Activated macrophages regulate the course, locality, duration and severity of inflammation. During the course of inflammation, distinct macrophage phenotypes have been observed. M1-macrophages are believed to be involved in the initiation and propagation of inflammation while M2 macrophages are apparently involved in the resolution of the inflammatory process. Therefore, identifying the regulatory mechanisms of macrophage phenotypic specification can be useful clinically to mitigate tissue damage and foment repair caused by dysregulated or persistent inflammatory conditions. Here we show that NOS1 regulation of suppressor of cytokine signaling-1 (SOCS1) stability in macrophages as a critical effector of macrophage phenotypic specification thereby indicating that NOS1 may be a clinically relevant drug target to suppress chronic inflammatory conditions. Further, increased amounts of SOCS1 in NOS1-/- macrophages leads to decreased p38MAPK activity, which impairs expression of M1 signature markers but not M1 genes. These data illustrate the molecular checkpoints involved in homeostatic macrophage polarization and suggest new therapeutic strategies to prevent inflammatory responses.

Biography:

Abstract:

We investigated the anti-influenza virus activity of Acacia nilotica and possible mechanism(s) of action in vitro. We found that Acacia nilotica has anti-influenza-virus activity, and both pre-incubation of virus prior to infection and post-exposure of infected cells with Acacia nilotica extract significantly inhibited virus yields. Influenza-virus-induced hemagglutination of chicken red blood cells was inhibited by Acacia extract treatment, suggesting that Acacia can inhibit influenza A virus infection by interacting with the viral hemagglutinin. Furthermore, Acacia extract significantly affect nuclear transport of viral nucleoprotein (NP). To best of our knowledge, this study revealed for the first time that Acacia nilotica extract can inhibit both viral attachment and replication and offers new insights into its underlying mechanisms of antiviral action.

The fruit husk ofAcacia nilotica collected from Sudan and Extracted with70% methanol.   The crude extract was screened for its cytotoxicity against MDCK cell line by alamar Blue assay and WST-1 assay. Antiviral properties of the plant extract was determined bycytopathic effect inhibition assay and virus yield reduction assay(plaque assay). Time of addition assay, and nuclear export mechanism were also performed.

• Autoimmune Diseases
  Viral Immunology: Emerging and Re-emerging Diseases
  Immunotherapy & Cancer Immunotherapy: From Basic Biology to Translational Research
  Immunology and Diabetes
  Vaccines and Immunotherapy
  Allergy and Asthma
  Mucosal immunology

Location: Berlin