Keynote Talks

Abstract

Probiotics are “good” bacteria present in the digestive tract, mainly from Lactobacillus and Bifidobacterium. They have an important role in digestion, but they also educate our immune system to react properly in order to protect us. In the allergic disease, probiotics reduce the development and activity of Th2 lymphocytes.
Probiotics include live bacteria and yeast present in our gut and foods. How they produce immunomodulatory effects is not completely known. Proteins can traverse the epithelial barrier of the gastrointestinal tract. Transcellular movement of antigen through the epithelial cell by endocytosis is mediated by interferon-g (Buning et al. 2005), allowing effective presentation of food antigens to the immune response and inducing oral tolerance and not inappropriate immune reactivity to that antigen. Interferon-g has been shown to be reduced in infants with cow’s milk allergy (Pohjavuori et al. 2004). Probiotics can strengthen the transport of molecules, rendering the gut ‘less leaky’ (Baumgart & Dignass, 2002; Qin et al. 2005).
The first studies shown to play a prophylactic role for allergy. A comparison of formula-fed v. breast-fed infants has shown a lower incidence of allergies in the breast-fed infants that correlates with higher levels of bifidobacteria (Kalliomaki et al. 2001; Watanabe et al. 2003). This finding suggests that particular organisms may be able to dictate the allergic potential of an individual. The use of probiotic therapy to prevent allergic disease (reducing the incidence of atopic eczema) has been demonstrated in two studies using a probiotic Lactobacillus rhamnosus GG in neonates. Unfortunately, these positive results have not been repeated in studies with older children and young adults.
There were performed studies for allergic rhinitis treated also with probiotics. Wang et al. (2004) assessed the effect of L. paracasei on perennial allergic rhinitis of at least 1 year duration and specific IgE for house dust mite has shown no clinical improvement of symptoms, although the probiotic group did report an improvement in quality of life. In pollen allergy less-promising results were demonstrated: L. rhamosus given 2. 5 months before the pollen birch season, 1 month during the season and for 2 months after the season. Both respiratory and eye symptoms did no differed between the probiotic and placebo groups. In addition, the probiotic group used more medication over the birch-pollen season compared with the placebo group (P = 0. 06) (Helin et al. 2002). A 2016 meta-analysis for the therapeutic effect of probiotics in allergic rhinitis provided significant evidence of beneficial clinical and immunologic effects of probiotics in the treatment of AR, especially with seasonal AR and LP-33 strains, despite high variability among the studies ( Güvenc et al). Although there is valid scientific evidence in vitro, there is no sufficient information to suggest the use of specific probiotics in allergy and asthma prevention.
In summary, probiotics have demonstrated an ability to prevent the induction of allergic symptoms, particularly that of atopic dermatitis, in high risk infants and in allergic rhinitis. This cannot be readily repeated in individuals already exposed to a particular allergen especially with respiratory symptoms. The ability of probiotics to regulate the induction of atopic dermatitis.

Biography

Diana Deleanu, Professor, Head of Department of Immunology, with experience of teaching this subject for 20 years. It is the originator of Allergology and Immunology compulsory education in UMF Cluj-Napoca. She has held courses in all faculties of medicine and dentistry in Iuliu Hatieganu University of Medicine and Pharmacy and other universities in the Romania. She contributed to courses for students of Medicine. The research translates into 10 grants and numerous national and international clinical trials. Subject research mainly refers to allergy and immunologic disease. She performed the first studies of epidemiology in allergic diseases in Romania. Diana Deleanu is the President of Romanian Society of Allergology and Clinical Immunology 2006 and she is the editor in chief of the Romanian Journal of Allergy and Clinical Immunology.


Speaker
Diana Deleanu / Iuliu Hațieganu University of Medicine and Pharmacy
Romania

Abstract

Infectious diseases caused by multi-cellular nematode parasites are a challenging global problem that relies heavily on host immune responses. The parasites on the other hand do not give-up and battle with strategies to effectively modulate immune responses. In such complex nematode diseases, the shuttle between the dynamics of health and disease of the host is dependent on the availability of efficacious diagnostic tools and preventive vaccines. Hence, in our research Centre at Anna University, we have studied the implications of such parasite-led immunological changes for four decades in the Human Lymphatic Filarial (LF) disease model – leading to translational immunological research resulting in immunodiagnostics and immuno-prophylactics. Recently, we have also ventured into immuno-target characterization for vaccine and drug development. The following work gives a summary of our progress in recent research work.
We have embarked on the immunological finding that filarial nematodes down-regulate host immune system through secretion of antioxidant and detoxification enzymes like glutathione-S-transferases (GSTs), thioredoxin etc., and these GSTs catalyse the conjugation of glutathione to xenobiotic and other endogenous electrophiles and are essential for their long-term survival in lymph tissues. Earlier studies have also shown Wuchereria bancrofti GST (WbGST) to be a potential vaccine target. Hence, to structurally characterize this immunotarget, we solved the structure of WbGST along with its cofactor GSH at 2.3Å resolution by X-ray crystallography methods and visualized potential epitopes. Further, structural comparisons against host GST revealed distinct differences in the substrate binding sites and were more substrate/solvent accessible. The structure also suggested the presence of putative non-catalytic binding sites that may permit sequestration of endogenous and exogenous ligands. Hence, the obtained information regarding crucial differences in the active sites can be utilized for the design of novel parasite specific inhibitors. We also evaluated the inhibition of WbGST and its variants by antifilarial and diethylcarbamazine (DEC) through kinetic assays. In a separate study, we also explored the immunomodulatory capabilities of DEC. In this regard, our study extends the current understanding of DEC’s mechanism of action against parasites and presents its immunomodulatory mechanism as a synergistic feature for microfilaria clearance in LF pathology.
We already developed various antigen/antibody based immunodiagnostic methods using a parasite-mf-surface protein WbSXP-1 identified from Wuchereria bancrofti. A rapid field applicable immunoassay kit (2 min) for diagnosis and surveillance is currently available for commercial screening. To augment this effort, we have a functional single-chain fragment variable (scFv) specific for filarial Wuchereria bancrofti SXP-1 (Wb-SXP-1) antigen was constructed for the diagnosis of active filarial infection, as an alternative to the production of complete antibodies using hybridomas. The variable heavy chain (VH) and the variable light chain (kappa) (Vκ) genes were amplified from the mouse hybridoma cell line and were linked together with a flexible linker by overlap extension polymerase chain reaction (PCR). The ScFv construct (Vκ-Linker-VH) was expressed as a fusion protein with N-terminal His tag in Escherichia coli and purified using immobilized metal affinity chromatography (IMAC) without the addition of reducing agents. Immunoblotting and sandwich enzyme-linked immunosorbent assay (ELISA) were used to analyze the antigen binding affinity of purified scFv. The purified scFv was found to recognize recombinant and native Wb-SXP-1 antigen in microfilariae (Mf)-positive patient sera. The affinity of scFv was comparable with that of the monoclonal antibody. The development of recombinant scFv to replace monoclonal antibody for detection of filarial antigen was achieved.
To further enhance the efficiency of the scFv against rWb-SXP1 and to recognize circulating filarial SXP-1 antigen, a DNA segment for in vitro protein expression was constructed. A simple procedure was developed to create diverse libraries of scFv based on a single DNA framework with all the requisites for an in vitro protein synthesis and ribosomal display technique. Random mutations were incorporated by using excessive MgCl2 during PCR and the presence of errors in the amplicons were confirmed by sequencing. The amplicons were In Vitro transcribed and translated and the products were used in ribosome display technique. Sandwich ELISA technique was devised to detect the Kd value between WbSXP1 and native scFv (His tagged) with Anti-His Biotinylated antibody as capture antibody and Streptavidin ALP conjugate as detection antibody. The Kd value was identified as 2.593 X 10-7M. Screening by ribosome display was conducted using WbSXP1 concentrations 10 fold lesser than the Kd value of native scFv. After the display, the mRNA sequences were reverse transcribed to cDNA, amplified and sequenced. Additional cycles of ribosome display were continued to segregate the evolved sequences for augmented affinity for rWbSXP1. Evolved sequence with six mutations from the native scFv was identified at the end of this technique. Reactivity with asserted clinical samples of endemic normals (EN), microfilariaemic (MF), chronic pathology (CP) and non-endemic normals (NEN) showed significant augment (p<0.0001) in reactivity to MF samples with evolved scFv in comparison to wild-type scFv. This evolutionary method coupled with ribosome display has facilitated us to improve the reactivity of the scFv without diminishing the specificity.

Biography

Perumal Kaliraj is Currently working as ICMR (Indian Council of Medical Research) Emeritus Medical Scientist. He worked as professor for nearly 20 years and as director of Centre for Biotechnology, and also Dean and Vice-Chancellor of Anna University, Chennai, India. His application-oriented research in combating filariasis has resulted in two commercial products along with three awards of Indian patents. As a member of WHO filarial genome project, he pioneered the development and characterization of several vaccine and drug targets for global elimination of filariasis. He is a recipient of various awards including the prestigious ones from ICMR and Parasitology Society. He has been elected as Fellow by Biotechnology Research Society of India and National Academy of Biological Sciences. The work which is presented here is a cumulative research work that was done over a period of four decades (since 1976).


Speaker
Perumal Kaliraj / Anna University
India

Abstract

Using CAGE transcriptomics we redefined the transcriptional regulatory dynamics of differentially activated classical (M1-IFNγ) or alternative (M2-IL-4/IL-13) macrophages and identified new genes and noncoding RNA species as potential targets for host-directed drug therapy for tuberculosis. We identified Batf2 as a transcriptional inducer of inflammatory responses during M. tuberculosis (Mtb) infection in mice and showed that BATF2 is a predictive biomarker for tuberculosis disease in humans. Additionally we demonstrate that non-coding microRNAs, miR-143 and miR-365, promote the intracellular growth of M. tuberculosis in alternatively IL-4/IL-13 activated macrophages by differentially targeting of c-Maf, Bach-1 and Elmo-1. We further demonstrated that Mtb exploits the host cholesterol pathway for its survival and we were able to increase host protection against tuberculosis by reducing cholesterol using statins. Mechanistically, statins increased phagosomal maturation and autophagy as host-protective functions to contain and reduce Mtb growth within macrophages. Here we present a proof-of-concept clinical trial to evaluate whether statins, widely used cholesterol-lowering drugs, could be employed as a repurposed drug for host-directed drug therapy in tuberculosis. In summary, targeting Batf2, miR-143 and miR-365 together with repurposed drugs such as statins offers possible adjunctive host-directed drug therapy that may reduce the burden and pathological inflammation of tuberculosis.

Biography

Reto Guler completed his PhD in Immunology from the University of Geneva, Switzerland (2003). His work was recognized by the Swiss Tuberculosis award. Currently he is an associate member of the Institute of Infectious Disease & Molecular Medicine (IDM), University of Cape Town, South Africa and the coordinator of the international PravaTB consortium that recently received a prestigious 4.9 million Euro award from EDCTP to conduct a clinical trial investigating the use of statins to prevent chronic lung inflammation and potentially TB relapse. He has published more than 43 papers including publications in Nature, Science, Immunity and PNAS.


Speaker
Reto Guler / University of Cape Town
South Africa

Sessions:

Scientific Sessions

Abstract

Since 2005, Campylobacter infections, caused particularly by Campylobacter jejuni have become the most commonly cause of human bacterial gastroenteritis in European Union. The broiler meat has been demonstrated as main source of infection. Immune system of broiler is inefficiently activated against C. jejuni colonization. Moreover, the expression of keys antimicrobial peptide genes is significantly downregulated by C. jejuni in broilers. Lactobacillus spp. as probiotic strains appears to be promising therapy, because several studies observed that probiotic bacteria can modulate the course of inflammation. The aim of this study was to evaluate the influence of Lactobacillus reuteri B1/1 on the relative expression of selected cytokines and defensin in cecum of broilers challenged with Campylobacter jejuni CCM6189. Forty eight one day-old chicks were divided into 4 experimental groups: control (C), L. reuteri (LB), C. jejuni (CJ), and L. reuteri + C. jejuni (LBCJ). L. reuteri at the concentration of 109 CFU was administered daily per os to selected groups from day 1 to day 7 of the experiment. C. jejuni was administered on day 4 by dose of 1x108 CFU to selected groups. Samples for isolation mRNA of target genes were collected 4 and 7 days after infection by C. jejuni. Homogenisation and isolation of total RNA was done. Amplification and detection of specific products were performed using CFX 96 RT system (Bio-Rad, USA) with predefined program. L. reuteri influenced expression of selected genes in cecum, thereby increasing the capacity of the immune system to react to the presence of C. jejuni.

Biography

DVM. Viera Karaffová, PhD. - researcher; scientific focus: molecular methods, immunology, bacteriology; leading the organization and implementation of experiments. She has published 18 papers in CC journals and has been investigator in more than 5 projects and head of 1 running project (VEGA č. 1/0112/18-˝Monitoring the immunological properties of new potential probiotic lactobacilli in in vitro and in vivo conditions of Campylobacter jejuni infection in chickens”). In 2018 she was awarded a scientific qualification level IIa from Slovak academy science.


Speaker
Viera Karaffová / University of Veterinary Medicine and Pharmacy, Slovakia

Abstract

The ability of cacwrous adsease to infect human body and subsist in it like a parasite is now aut of the main stream of the discoveries of the diology, epideviology, genetics, immunology and pathogenesis of this disease. Main goal of this message is to present more exhaustive information about ethnic differences in genetic immunity to cancerous disease. The data about the subsistence of the disease in 125 ethnoses around the World have been analyzed. The groups of most immune and most susceptible ethnoses have been revealed. Causative agent of this disease is a specific eucariotic genomic parasite, spreading amongst humans via its intrusion in the genomes of susceptible organisms. The Intrusion of cаncerous genes is performing by contaminated human gametes, either by the sperm or by the egg. .The parasite subsistence of human cancerous disease is functioning at the expense of substances and functions derived from the body of its prey. .This trait is cruial for the progression of cancerous disease within a human body but intensive nutrition of developed cancerous tissues leads contaminated person to the loss of his body weight. The subsistence is provided with the possession by cancerous subjects of genetic immunity to the victim's immune defense and cell regulation. These new notions provide framework and landmarks for the detection and discovery of genomic roots of cancerous disease and encourage new proposals for its healing and prevention, as well as for the discovery of the origin and evolution of cancerous disease.

Biography

Sergey N. Rumyantsev was born and educated in Yaroslavl, Russia. He has earned his MD at Medical Military Academy, Leningrad, Russia and completed his Ph.D. at the age of 33 years from Medical Military. Research Institute, Sverdlovsk, Russia. Now he is research director of Andent Inc., New York, USA. He has published 5 innovative scientific monographs and more than 30 papers in reputed journals. Among his publications, there should be especially noted the monographs «Biological weapon: A Terrible Reality? Profound Delusion? Skillfull Swindling?” (2008) and “Hereditary Immunity: Fundamental Principles and Exploitation in Life Study and Health Care” (2008) as well as the papers entitled “Functions of Hereditary Immunity and Xenogamy in Cancer Origin and Pandemic Spread” (2011), “Evolutionary Adaptations of Human Cancer for Parasitic Life” (2013) and «Parasite subsistence of human cancer» (2018).


Speaker
Sergey N. Rumyantsev / Andent Inc.,
United States

Abstract

Chemokines are proteins released from chondrocytes and/or synovial fibroblasts of osteoarthritis patients. We investigated the possible association between promoter polymorphisms rs1024611 and rs4586 in exon 2 of the chemokine (C–C motif) ligand 2 (CCL2) gene and knee osteoarthritis (KOA). DNA was obtained from 300 primary KOA patients and 300 controls. Polymorphisms rs1024611 and rs4586 were detected by PCR-RFLP method. The effect of serum levels of these polymorphisms were examined by ELISA.The rs1024611 A/G promoter polymorphism was associated with KOA [genotype frequency, p < 0.007; allele frequency, p < 0.01]. Significant association was observed between the G carrier of the rs1024611 polymorphism and primary KOA patients (p=0.01). Haplotype frequency analysis revealed a significant difference (p <0.02). The CCL2 serum level of subjects with G carrier of rs1024611 A/G promoter polymorphism was statistically higher than subjects with non-G carrier.Further in relation with clinical severity of KOA, we observed significant association of the G carrier of the rs1024611 A/G promoter polymorphism with both VAS (p<0.01) and WOMAC score (p<0.05).SNP rs1024611 of CCL2 gene is convincingly implicated in genetic factor of KOA. This may be due to an association of CCL2 with disease progression, or an influence of genotype on age of onset of KOA, hence who develop the disease earlier in life may have more years at risk for progression.The G carrier of the rs1024611 A/G promoter polymorphism was found to be associated with primary KOA, and could be a susceptibility factor in the development of primary KOA.

Biography

Amar Chandra Sharma has completed his PhD from King George’s Medical University, India in 2018. He has been awarded Post Doctoral Research Assoiate fellowship by Indian council of medical Reseacrh (ICMR). Currently He is the Research Associate of Department of Orthopaedic Surgery under the guidence of Prof. Rajeswar N. Srivastava. He has published more than 7 papers in reputed journals.


Speaker
Amar Chandra Sharma / King George’s Medical University
India

Abstract

Cytokines are protein molecules that help regulate and direct the immune system. Difficulty to translate the promise of cytokine therapies to benefit patients are because of toxicities, poor pharmacokinetics or suboptimal pharmacodynamics. We have engineered cytokines using polymer technology to enable viable medicines. NKTR-214 is in Phase 3 clinical trials and a key example of how polymer conjugation can bias the well-known IL-2 receptor pathway to favor CD8 T cell tumor infiltration over Tregs. On the other hand, NKTR-255 an IL-15 receptor agonist stimulates NK cells. Each agent is conjugated in unique ways to elicit desirable and controlled pharmacological and immunological outcomes.

Biography

Loui Madakamutil is SVP and Head of Biology and Preclinical Development at Nektar Therapeutics. In this role, Loui is responsible for the discovery strategy of Nektar to deliver novel immuno-modulatory medicines in several therapeutic areas. Previously Loui was a Senior Director at J&J. Loui held appointment as the Site Head of Immunology at Takeda Pharmaceuticals in San Diego. Loui also spent five years in Immunology discovery at Celgene. He has taken several large and small molecule compounds into clinic. Loui did his Post-Doctoral training at the La Jolla Institute for Allergy and Immunology and has a PhD from University of Mumbai, India.


Speaker
Loui Madakamutil / Nektar Therapeutics
United States

Abstract

Introduction: Rheumatoid arthritis (RA) and chronic periodontitis (CP) are both inflammatory diseases characterized by severe inflammation of the related tissues. Patients with RA were reported to have poorer periodontal conditions like more gingival bleeding, higher probing depth (PD) and clinical attachment level (AL) or more missing teeth. TNF-α blockers used in the treatment of RA seemed to positively influence the immune response of the periodontium.
Aim: The case-controlled study shall verify if RA-patients under continuous medication with TNF-α blockers have better or worse periodontal health than non-RA patients with periodontitis.
Material and methods: 13 patients with RA and 13 age and sex-matched non-RA periodontitis patients were studied. In the RA-patients RA-medication and his duration were registered. In all patients gingival bleeding (GBI), plaque control record (PCR), bleeding on probing (BOP), PD, AL and the number of teeth were recorded. For all patients the severity and extent of periodontitis was stabilized respecting the classification system for periodontal diseases as well as serum level of C-reactive protein (CRP) were determined. Wilcoxon and Chi-square tests were performed for statistical analysis.
Results: RA-patients had significantly less BOP (15.38% vs. 27.23%, p=0.045). RA-patients had a tendency to lower PD-values (2.54mm vs. 3.15mm, p=0.068) and fewer sites with PD≥5 mm (6.00 vs. 17.46, p=0.099). Comparing severity and extent of periodontitis RA-patients had significantly better periodontal conditions (p=0.033). No significant influence of the duration of RA-medication was found.

Biography

Holger Jentsch is a professor at the University of Leipzig and one of the German specialists for periodontology and shows how periodontology can be integrated into everyday practice. He has decades of experience in the clinic and also in research with more than 150 publications. Jentsch has given more than 300 oral presentations in the field of periodontology considering antiinfective, antiinflammatory, antibiotic and regenerative therapy.


Speaker
Holger Jentsch / University of Leipzig
Germany

Abstract

Inflammasomes are multimeric protein complexes that are formed in a cell to orchestrate host defense mechanisms against infectious agents and physiological aberration. Assembly of the inflammasome complex is initiated by nucleotide-binding domain and leucine-rich repeat receptors (NLRs) or absent in melanoma 2 (AIM2)-like receptors (ALRs). NLRs and ALRs mediate host recognition of pathogen-associated molecular patterns (PAMPs) released during bacterial, viral, fungal, and protozoan infections, or danger-associated molecular patterns (DAMPs) released during cellular damage. Activated NLRs and ALRs, in most cases, recruit a bipartite protein known as ASC to engage caspase-1. NLR- and ALR-mediated caspase-1 activation drives pyroptosis/cytokine secretion and are largely beneficial to the host during an infection. However, these cytokines induced by endogenous danger signals trigger sterile inflammation, a risk factor for the development of autoinflammatory and metabolic diseases. Therefore, activation of the inflammasome must be finely controlled to avoid overt tissue damage. These regulatory activities are governed by scaffolding proteins and post-translational modifications, which together, tightly control and modulate inflammasome activation.

Biography

Thirumala-Devi Kanneganti, Ph.D. is the Vice Chair of Immunology and the Rose Marie Thomas Endowed Chair at St. Jude Children’s Research Hospital. She is listed by Thompson Reuters/Clarivates in the top 1% of immunologists in the world, based on citations per paper. Her lab has recently identified ZBP1/DAI as an innate sensor of influenza virus that triggers the NLRP3 inflammasome and programmed cell death pathways. Kanneganti has authored approximately 220 original peer-reviewed publications. She serves on numerous editorial boards and several national and international advisory and grant review committees. She is currently the Chair of the NIH Innate Immunity and Inflammation study section. She has received many awards including the AAI-BD Biosciences Investigator Award in 2015, Society for Leukocyte Biology (SLB) Dolph O. Adams award and Eli Lilly and Company-Elanco Research Award from the American Association of Microbiology (ASM), More recently, the International Cytokine & Interferon Socitey Awards Committee have chosen Kanneganti as one of the recipients of the 2018 Seymour & Vivian Milstein Award for Excellence.


Speaker
Thirumala-Devi Kanneganti / St. Jude Children’s Research Hospital
United States

Abstract

We have investigated the prophylactic and therapeutic efficacies of a designer hypoallergen DNA vaccine (MEM49) of shrimp tropomyosin in a mouse model of shrimp hypersensitivity, but the genes and pathways involved remain obscure. In this study, we aimed at identifying key modulatory mechanism of immunotherapy of this vaccine. Ileum from BALB/c mice prophylactically and therapeutically administrated with a MEM49-based DNA vaccine, as well as control mice were harvested and their RNA was extracted for RNA-sequencing using the Ion Torrent Proton Platform. Candidate pathways preferentially affected by pMEM49 immunization were identified by Gene Set Enrichment Analysis (GSEA) against 4872 immunologic signatures from ImmuneSigDB, cell type/tissue specific signatures from PaGenBase and our in-house database. Comparison of the RNA profiles of the vaccine-treated groups with positive control revealed significant repression on PAX5 expression but significant enrichment in gene sets concordant to augmented regulatory T cell and tolerogenic dendritic cell (tDC) activities. Specifically, IRF8 upregulation led to the induction of indoleamine 2,3-dioxygenase (IDO) competence and IL-27 expression in murine DCs. These in turn increased TGF- production and promoted IL-21 expression in T cells. Our data suggest that IL-21 can mechanistically inhibit IgE production via diminishing PAX5 expression in hypoallergen DNA vaccine treated mice. To conclude, pMEM49 immunization induces IL-27 and TGF--producing tDCs that activate regulatory and IL-21-producing T cells in controlling IgE synthesis via a PAX5-dependent manner. The transcriptomic analyses and candidate pathways described here provide clues to the key immuno-modulatory players of immunotherapy to benefit future mechanistic studies and immunotherapeutic designs.

Biography

Ka Hou Chu completed his PhD study at the Massachusetts Institute of Technology/Wood Hole Oceanographic Institution Joint Program in Oceanography. He is now a professor at the School of Life Sciences, The Chinese University of Hong Kong and was the first Director of the school. He is also an outstanding fellow of the Faculty of Science, and associate head of the New Asia College of the University. With primary research interests in molecular phylogeny and biogeography of marine organisms and seafood allergy, Chu has published over 200 papers. He serves as associate editor for three international journals.


Speaker
Ka Hou Chu / The Chinese University of Hong Kong
Hong Kong

Abstract

Eerging evidence suggest that microRNAs are involved in inflammatory process and cancer development during chronic inflammation. MiRNAs are differentially expressed in developing tissues, numerous cancers and some human diseases including Inflammatory Bowel Disease.
We assessed the expression of any miRs in distinct colonic anatomic locations, with the purpose of identifying potentially confounding changes related to location rather than pathology per se. Our retrospective study on patients with CRC indicates that the differential miRNA expression during UC perhaps contribute in the development of UC associated CRC at the rectosigmoid area. Interestingly, MicroRNA exhibit altered expression in the inflamed colonic mucosa of ulcerative colitis patients compared to non inflamed region of the same patient.
Further we observed SNPs in miR-196a-2 rs11614913 and miR-499 rs3746444 were associated with UC in north Indian population. We found the genotype that showed association with UC also altered the expression of respective miRNA in the patient harboring the genotype. There was correlation between associated genotype and altered miRNA expression.
First report to identify miR-200a as a significantly differentially expressed miR species in the UC patients involving rectosigmoid region. Altered cytokine and chemokine expression is considered to be a hallmark of ulcerative colitis. We demonstrated that miR-200a targets the expression of an important chemokine CXCL12. Upregulation of CXCL12 in the rectosigmoid region occurs due to downregulation miR-200a. We explored the possibility of using them as non invasive biomarker to assess the location of the disease and at different stages of the disease.

Biography

Jaishree Paul possesses thirty years of teaching and research experience in Jawaharlal Nehru University, New Delhi. She has 68 research papers to her credit, published in peer- reviewed international journals. She has authored two books. “Handbook of Disease causing Microbes” published jointly by Ane Books, Delhi and CRC Press (2016). “MicroRNA: Perspectives in Health and Diseases” published by CRC Press (Taylor and Francis) released in March, 2018. Among various awards and honors, she is a recipient of Visitor’s Research award by the president of India in 2016.


Speaker
Jaishree Paul / Jawaharlal Nehru University
India

Abstract

Introduction: Anti-apoptotic protein Bcl-2 prevents apoptosis through the mitochondrial pathway. High-level of Bcl2 is required for chronic lymphocytic leukemia cell (CLL) survival. Berberine (BBR) is an alkaloid that induces apoptosis of cancer cells via mitochondrial pathways. The aim of this study was to investigate the effect of Berberine on the Bcl-2 gene expression in peripheral blood mononuclear cells (PBMCs) of CLL patients compared to healthy subjects in vitro.
Materials and Methods: In this study, peripheral blood was obtained from 12 untreated CLL patients and 6 age-matched healthy subjects. PBMCs were isolated by ficoll separation and were cultured in two groups, treated with Berberine (25 μM) and untreated. The cells were incubated for 48 hours in cell culture conditions. Finally, Bcl-2 gene expression was investigated in both groups following RNA extraction and cDNA synthesis by Real time PCR using SYBR Green method.
Results: Bcl-2 gene expression levels in CLL patients which was treated with Berberine were significantly lower than untreated group (p<0.05), however no significant difference were observed in treated compare to untreated cells in healthy control group.
Conclusion: The results indicate that the apoptotic activity of Berberine may be mediated through the reduction of Bcl-2 mRNA expression level in leukemic cells of CLL. Considering the essential role of Bcl-2 in the survival of tumor cells, Berberine could be considered as a potential natural remedy for CLL for further studies.

Biography

Parviz Kokhaei has completed his PhD in 2006 from Karolinska Institutet in Stockholm, Sweden and postdoctoral studies in the same institute in 2008. His research interests include cancer Immunology and immunotherapy. Currently, he is a vice-president in Research and Technology at Semnan University of Medical sciences, Semnan, Iran. He is also affiliated to Karolinska as a researcher.


Speaker
Parviz Kokhae / Semnan Univrsity of Medical Sciences
Iran

Abstract

Investigated is justification for determining the total and specific immunoglobulin E in children and adult patients diagnosed with bronhial asthma.
In the study was included children and adults patients. Number of children included in the study was 35 and adults was 35. Control group included 20 subjects.
Patients were diagnozed with asthma by the pulmonary specialist, based on anamnesis, clinical findings, physical exam and functional diagnostic tests done at the University Clinical Center in Tuzla.
Total Ig E was determined by nefelometric method and skin test by Prick method was also performed on all of the subjects. Subjects which had incrased values of IgE, had also been tested for fecal parasites. Subjects which were positive for skin alergens were also tested for specific IgE on Hytec 288 instrument with ELISA method.
Following results were obtained: 97,14% (34) of child age subjects had increased total IgE, while 2,86% (1) of subjects had normal results. In the group of adult subjects 57,14% (20) of subjects had increased IgE, while 42,86% (15) had normal IgE.
All patients with incrased values of total IgE were tested negative for fecal parazites.
All child age subjects with positive Prick test had had also positive specific IgE except for pollen weeds, while this was not a case for all adult subjects.
The most frequent alergen in child age group was Dermatophagoides pteronyssinus and in adult group house dust.

Biography

Fejzo Dzafic, clinical immunologist. He is working at the University Clinical Center in Tuzla Department of Clinical Immunology. He has completed his PhD from Medical Faculty University of Tuzla, Bosnia and Herzegovina. He is Assistant Professor in Clinical Immunology at the Medical Faculty University of Tuzla, head of Chair Clinical Immunology, Immunohematology and Flow Cytometry of this faculty. He has published more than 20 papers in reputed journals. He had professional training in field of clinical immunology and allergy in the United States, Germany, Croatia, Bulgaria, Montenegro.


Speaker
Fejzo Dzafic / University Clinical Center Tuzla
Boznia and Hercegovina

Abstract

Rheumatic heart disease occurring as an epidemic in the tropical nations. It starts with a throat infection and repeated episodes provoke an immune mediated injury towards heart valves. After a latent period, the valves become calcified, leading to stenosis or regurgitant lesions. Early understanding of this process make an insight to prevent and halt this disease and enable to save the younger and middle aged populations from these valvular deformities. Researches are targeting on vaccination and lifelong prophylaxis, but focus on immunomodulation therapy may bring a better outcome in this crippling disease

Biography

Ramachandran Muthiah is a Consultant Physician & Cardiologist at Zion hospital, Azhagiamandapam, Kanyakumari District, India. He has published many papers in Cardiosource, American College of Cardiology Foundation, Case Reports in Clinical Medicine (SCIRP) and Journal of Saudi Heart Association. His special research is on Rheumatic fever and Endomyocardial fibrosis in tropical belts, Myxomas, Infective endocarditis, apical hypertrophic cardiomyopathy, Ebstein’s anomaly, Rheumatic Taussig-Bing Heart, Costello syndrome and Tetralogy of Fallot.


Speaker
Ramachandran Muthiah / Zion hospital
India

Abstract

Severe combined immunodeficiency (SCID), a rare PID, is poorly characterized in China. In this study, we retrospectively reviewed patients with SCID referred to our hospital from 2004 to 2017, and summarized their clinical manifestations and genetic features. Clinical features were summarized and outcome of each patient was traced from history records. Targeted gene capture combined with next-generation sequencing technology and Sanger sequencing were used to find out related gene mutation. The results showed that, among 725 patients with PID, 95 (13.1%) were diagnosed as SCID. The mean time of delay in the diagnosis was 2.76 months (range, 0.4-22 months). Fifty-six of the 95 patients (58.95%) died by the end of 2016 with the mean age being 8.55 months. Respiratory tract infections were the most common (83 cases, 87.37%) including pneumonia and upper respiratory tract infection. Gastrointestinal infection and oral candidiasis was found in 70 (73.68%) and 42 (44.21 %) patients, respectively. BCG complications occurred in 30 of the 66 patients who received BCG vaccination. Transfusion-induced GVHD occurred in 8 patients. Eight patients received HSCT, one survived, who was transplanted twice. Total 30 mutations in IL-2RG were identified in 42 patients, including 18 novel mutations. In conclusion, diagnosis of SCID has improved over the last decade in China. Complications of BCG vaccine are an important warning sign for the presence of SCID and account for significant morbidity during disease progression. Establishing more diagnostic centers dedicated to the care of PID will facilitate early, correct diagnosis and better care of SCID in China.

Biography

Tong-Xin Chen has completed his PhD from Shanghai Jiao Tong University School of Medicine, Shanghai, China and postdoctoral studies from Mie University, Japan. He is the director of department of allergy and immunology, Shanghai Children’s Medical Center, Shanghai ,China. He had published more than 40 papers as coresponding author.


Speaker
Tong-Xin Chen / Shanghai Jiao Tong University School of Medicine
China

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