Program Day 1

  • Utsunomiya University, Japan
  • Title:Melanocyte Activation Mechanisms and Rational Therapeutic Treatments of Solar Lentigos
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To characterize the pathobiology of solar lentigos (SLs), analyses by semiquantitative RT-PCR, Western blotting, and immunohistochemistry revealed the upregulated expression of endothelin (EDN)-1/endothelin B receptors (EDNBRs), stem cell factor (SCF)/c-KIT, and tumor necrosis factor (TNF)α in the lesional epidermis, which contrasted with the downregulated expression of interleukin (IL) 1α. These findings strongly support the hypothesis that previous repeated UVB exposure triggers keratinocytes to continuously produce TNFα. TNFα then stimulates the secretion of EDNs and the production of SCF in an autocrine fashion, leading to the continuous melanogenic activation of neighboring melanocytes, which causes SLs. A clinical study of 36 patients with SLs for six months treated with an M. Chamomilla extract with a potent ability to abrogate the EDN1-induced increase in DNA synthesis and melanization of human melanocytes in culture revealed a significant improvement in pigment scores and color differences expressed as L values. Another clinical study using a tyrosinase inhibitor L-ascorbate-2-phosphate 3 Na (ASP) demonstrated that L values of test lotion (6% APS)-treated skin significantly increased in SLs and in non-lesional skin with a significantly higher ΔL value in SLs when compared with non-lesional skin. The sum of these findings strongly suggests that combined topical treatment with EDN signaling blockers and tyrosinase inhibitors is a desirable therapeutic choice for SLs.

Dr. Genji Imokawa (Ph.D.-medicine) now is Professor of Utsunomiya University, Center for Bioscience Research and Education as well as Visiting Professor of Chubu University, Research Institute of Biological Functions and of Ohio University, Edison Biotechnology Institute. Board of Directors in Japanese Society for Ceramide Research and Japanese Medical Society for Skin Aging and Council member for Japanese Medical Society for Anti-Aging. Research Activities: More than 175 original English papers including EMBO Journal, J Clinical Invest, J Cell Sci, Cancer Res, Am J Pathol, FASEB J, J Biol Chem, J Pathol and J Lipid Res; Research Field: Photo-aging/ Fibroblasts, Atopic Dermatitis/Sphingolipid Metabolism, Melanogenesis/Melanocyte Biology, Keratinization/Keratinocyte Biology.

  • USA
  • Title:Recent Developments in Cell-SELEX Technology for Aptamer Selection
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SELEX technique is employed to select aptamers against wide range of targets. The in vitro method of aptamer selection using live cells as the target is referred as CELL-SELEX. The use of aptamers as therapeutic and diagnostic agents is rapidly evolving, selection techniques such as Cell-SELEX could be beneficial in identifying aptamers when the target is in its native conformation and without prior information of the cognate target, thereby bringing the aptamer development one step closer to the clinic. The presentation provides a comprehensive description on the development of aptamers through various cell-SELEX methods. In addition, it pinpoints the advantages and limitations of the cell-SELEX process and its variants. The given information can be valuable for the design and development of futuristic oligonucleotide based diagnostics and therapeutics work.

Dr Harleen Kaur has been in the pharmaceutical industry for almost 8 years and most recently led the analytics and drug product tech transfer projects for two biologics products while working at AstraZeneca, USA. Prior to this, she worked in R&D division of Fujitsu Asia Pte Ltd in Singapore where she worked on aptamer development and played an integral role in identifying and purifying aptamers against different protein targets in collaboration with National University of Singapore, Agency of Science Technology and Research Singapore, and Japanese diagnostic enterprise Sysmex. In her current role, Dr Kaur is leading a team of analytical scientists at Aurobindo Biologics and her responsibilities include the method development, method qualification and method transfer for different biosimilar products. Dr Kaur completed her PhD in chemical and biomolecular engineering department at National University of Singapore.

  • Center for Integrative Medical Sciences ,Japan
  • Title:Role of mRNA Decay in Tissue Development and Homeostasis
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mRNA decay is required for many biological events, and dysregulation of the mechanism leads to disorders, including cancer, neurodegenerative diseases and diabetes. A shortening of poly(A) tails (deadenylation) triggers mRNA degradation, that is mainly mediated by the CCR4-NOT complex.
Liver development involves dramatic gene expression change mediated by transcriptional and post-transcriptional control. We generated mice lacking a Cnot3 gene, encoding an essential subunit of the CCR4-NOT complex, in liver from a neonatal stage (Cnot3-LKO mice). Hepatocyte death and inflammation were observed in the livers of Cnot3-LKO mice. Gene expression analysis showed increased expression of immune response-related, cell cycle-regulating, and immature liver genes in the livers of Cnot3-LKO mice. In contrast, genes, which are relevant to liver functions, such as oxidation-reduction and lipid metabolism, decreased, indicating impaired liver functional maturation. Highly expressed mRNAs possessed elongated poly(A) tails and were stabilized in the livers of Cnot3-LKO mice. Similar results were obtained when we suppressed the CCR4-NOT complex in adult mouse liver. These data suggest that the CCR4-NOT complex-mediated mRNA decay plays a critical role in liver maturation and function, providing novel insights into tissue development and homeostasis.

Dr. Toru Suzuki is a Senior Researcher at RIKEN, Center for Integrative Medical Sciences from 2016. Main research interests are roles of posttranscriptional mechanisms in biological processes.
He received Ph.D. from University of Tokyo in 2001. He became Research Associate at Division of Oncology, Department of Cancer Biology, Institute of Medical Sciences, University of Tokyo and did research to 2012. He moved to Okinawa Institute of Science and Technology Graduate University as a Staff Scientist at Cell Signal Unit in 2012 and worked until 2016.

  • Ludwik Hirszfeld Institute of Immunology & Experimental Therapy, Poland
  • Title:New Insights into MS Pathomechanisms: On the Track to Control Inflammation and Neurodegeneration
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Multiple sclerosis (MS) is a chronic disorder characterized by multifocal inflammatory infiltrates (T cells, B cells, macrophages) within the central nervous system (CNS) and concomitant degradation of myelin, oligodendrocytes and axons, along with reactive microgliosis. Disease background is thought to include two overlapping processes: polyphasic myelin destruction (inflammatory demyelination) and progressive axonopathy (neurodegeneration) with little capacity for repair. The pathology is generally believed to reflect autoimmune attack upon myelin auto-antigens but the mechanisms resulting in the escalation of the autoimmune response and leading to the damage of white and gray matter in the CNS have not been so far fully clarified.
Lipid antigens are substantial myelin components and they also may constitute potential candidates for autoimmune attack in MS. We have recently explored the seem to be role of bioactive lipids, particularly ceramide, in the pathomechanism of autoimmune demyelination in MS. Specifically, we examined TNF- and IFN- effect, the two Th1 pro-inflammatory cytokines known to be accumulated in MS brain, upon a human oligodendroglioma (HOG) cell line. Our results suggested an exosome-mediated new mechanism of synergistic cytotoxicity of TNF- and IFN-. Ceramide-laden exosomes, when released from stressed or cytokine-targeted oligodendrocytes in vivo, may “broadcast” the cell death signal and promote the immune response that occurs under demyelinating conditions in the CNS. For this reason exosomes offer new molecular insights into MS pathology and perhaps could be used in the future as bioactive markers for the disease activity. On the other hand, it is well known that ceramide play a central role in sphingolipids metabolism which intricate scenario with numerous potential therapeutic targets, e.g. “engineered” exosomes can be used as an efficient vehicles for delivery of therapeutic agents across the blood-brain barrier.
A complex and heterogeneous picture of MS immunopathology may suggest the presence of various immunoregulatory abnormalities in this disease. These may result from disturbed functional interactions of many cellular components of the immune system, especially regulatory T cells. Natural killer T (NKT) cells may perform major regulatory functions in immunity, however their function in MS is not yet fully understood. In our studies, we identified glycosphingolipid (GSL)-reactive CD1-restricted lymphocytes especially those of the NKT and NKR+ phenotype and with T cell regulatory functions. GSL-driven anergy of circulating lymphocytes in MS suggests that the altered immune response in MS is via robust invariant NKT (iNKT) activation with potent cellular and cytokine activities. Diverse GSLs including the endogenous myelin acetylated-galactosylceramides (FMCs) can drive activation critical to controlling CNS inflammation and fostering myelin repair. Rendering iNKT-cells hyporesponsiveness to an endogenous GSL is a novel insight into diseases manifesting aberrant iNKT-cell activation. Furthermore, the state of anergy following stimulation with the auto-antigen FMC-7 may have significant clinical implications, according to the theory of antigen-specific therapy of autoimmune diseases.
An equally important factor in the pathology of MS, apart from (sub)acute demyelination, is progressive axonal and neuronal damage, resulting in accumulating neurological deficit and disability. Earlier reports indicate that calpain has been implicated in MS autoimmune mechanism, including demyelination, axonal damage, loss of neurons and oligodendrocytes and modulation of proteins involved in apoptotic pathways. We hypothesized that this Ca2+ dependent cysteine protease plays a key regulatory role in immune activation of MS pathology and its deactivation (inhibition) causes remission with control of autoimmune inflammation and neurodegeneration. Our studies yielded new findings regarding the mechanism of progressive MS that have implications for potential treatment. Based on two primary culture models  rat and human  we identified calpain as a key neuron injury signal driving the toxic component of reactive microgliosis. Specifically, we determined that calpain, released upon neuron damage, activates microglia to produce reactive oxygen species and nitric oxide that are selectively toxic to neurons. Our findings indicate that damaged neurons themselves are culpable in propagating further neurotoxicity with pro-inflammatory signals to microglia. These studies provide much needed insight into the nature of progressive phase of MS, with emerging putative preventive and therapeutic options. These novel findings (e.g., targeting calpain inhibition) may provide valuable insight into the mechanisms by which Th1 cells elicit neurodegeneration and appear promising in the treatment of progressive types of MS but also other neurodegenerative disorders.

2019 Habilitation: Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland
2003 Ph.D.: Institute of Immunology & Experimental Therapy Polish Academy of Sciences, Wroclaw, Poland
1997 Master of Science & Engineer: Wroclaw University of Technology, Department of Chemistry, Wroclaw, Poland
Professional Experience:
since 1997 Ludwik Hirszfled Institute of Immunology & Experimental Therapy,
Polish Academy of Sciences, Wroclaw, Poland
2012 and 2014-2016 – Medical University of South Carolina, Charleston, SC, USA
2010-2011 – Heinrich Heine University, Düsseldorf, Germany
2004-2010 – Georgia Regents University, Augusta, GA, USA
Honors and Awards:
2016 Certificate of the Polish-American Fulbright Commission received at the Ministry of Science and Higher Education in recognition of merits to promote Polish science and culture and to strengthen friendships between the peoples of the Republic of Poland and the United States of America through participation in the program of Fulbright Senior Award 2015-2016.
2015 Fulbright Senior Award nomination by the Polish-U.S. Fulbright Commission approved by J. William Fulbright Foreign Scholarship Board, Washington, DC, USA.
2014 Fellowship award approved by the Kosciuszko Foundation, New York, NY, USA.
2011 Du Pré Grant award approved by the Multiple Sclerosis International Federation, London, United Kingdom.
2007 Wroclaw Medical University Rector’s award for scientific publication, conducted in collaboration between Medical University and IIET, published in 2006 in the journal of the highest IF value (Galactosylation of IgG from rheumatoid arthritis [RA] patients-changes during therapy; Glycoconj. J. 23, 463-471, 2006).
2003 Award for Ph.D. dissertation, Institute of Immunology & Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Professional Memberships:
since 2016 Member of the Fulbright Scholar Alumni Program administered by the Council for International Exchange of Scholars, a division of the Institute of International Education, Washington, DC, USA
since 2015 Member of the Kosciuszko Foundation Research Alumni Program, Warsaw, Poland
since 2012 Member of the Multiple Sclerosis International Federation Research Alumni Program, London, United Kingdom
since 2008 Member, The International Society of Neuroimmunology
Selected Publications:
M. Podbielska, J. O’Keeffe, E. L. Hogan Autoimmunity in multiple sclerosis: role of sphingolipids, invariant NKT cells and other immune elements in control of inflammation and neurodegeneration J. Neurol. Sci. 385, 198-214, 2018.
N. M. Trager, J. T. Butler, J. Harmon, J. Mount, M. Podbielska, A. Haque, N.L. Banik and C.C. Beeson. A Novel Aza-MBP Altered Peptide Ligand for the Treatment of Experimental Autoimmune Encephalomyelitis. Mol. Neurobiol. 55(1), 267-275, 2018.
M. Podbielska, Z.M. Szulc, E. Kurowska, E.L. Hogan, J. Bielawski, A. Bielawska, N.R. Bhat. Cytokine-induced release of ceramide-enriched exosomes as a mediator of cell death signaling in an oligodendroglial cell line. J. Lipid Res. 57(11), 2028-2039, 2016.
M. Podbielska, A. Das, A. W. Smith, A. Chauhan, S. K. Ray, J. Inoue, M. Azuma, K. Nozaki, E.L. Hogan and N.L. Banik. Neuron-Microglia Interaction Induced Bi- directional Cytotoxicity Associated with Calpain Activation. J. Neurochem. 139(3), 440-455, 2016.
J. O’Keeffe, M. Podbielska, E.L. Hogan. Invariant natural killer cells and their ligands: focus on multiple sclerosis. Immunology 145, 468-475, 2015.
M. Podbielska, N.L. Banik, E. Kurowska, E.L. Hogan. Myelin Recovery in Multiple Sclerosis: The Challenge of Remyelination. Brain Sci. 3, 1282-1324, 2013.
E.L. Hogan, M. Podbielska, J. O’Keeffe. Implications of lymphocyte anergy to glycolipids in multiple sclerosis (MS): iNKT cells may mediate the MS infectious trigger. J. Clin. Cell. Immunol. 4, 144, 2013.
C. Gately, M. Podbielska, T. Counihan, M. Hennessy, T. Leahy, A.P. Moran, E. L. Hogan, J. O’Keeffe. Invariant natural killer T-cell anergy of circulating lymphocytes to myelin polyacetylated-β-galactosyl-ceramides in multiple sclerosis. J. Neuroimmunol. 259 (1-2), 1-7, 2013.
M. Podbielska, H. Krotkiewski and E.L. Hogan. Signaling and regulatory functions of bioactive sphingolipids as therapeutic targets in multiple sclerosis. Neurochem. Res. 37, 1154-1169, 2012.
M. Podbielska, S.B. Levery and E.L. Hogan. The structural and functional role of myelin fast-migrating cerebrosides: pathological importance in multiple sclerosis. Clin. Lipidol. 6(2), 159-179, 2011.
M. Podbielska, S. Dasgupta, S.B. Levery, W.W. Tourtellotte, H. Annuk, A.P. Moran, E.L. Hogan. Novel myelin penta- and hexa-acetyl-galactosyl-ceramides: structural characterization and immunoreactivity in cerebrospinal fluid. J. Lipid Res. 51(6), 1394-1406, 2010.
M. Podbielska and E.L. Hogan. Molecular and immunogenic features of myelin lipids: incitants or modulators of multiple sclerosis? Mult. Scler. 15(9), 1011-1029, 2009.

  • Can Tho University of Medicine and Pharmacy, Vietnam
  • Title:Analysis of the Length Polymorphisms in Sequence-Tagged-Site sY1291 on Y Chromosome in Vietnamese men of Infertile Couples.
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Our group has been working on the implication of adherent-invasive Escherichia coli (AIEC) in the etiology of Crohn’s disease (CD). We have showed that AIEC abnormally colonize the intestinal mucosa of CD patients, adhere to and invade intestinal epithelial cells (IECs), survive and replicate within macrophages, promote pro-inflammatory cytokine production, and colonize the gut and induce intestinal inflammation in genetically susceptible mouse models. We also showed that upon AIEC infection, autophagy is activated in host cells to restrain AIEC replication and to inhibit AIEC-induced inflammation. We showed recently in vitro and in vivo that activation of the metabolic stress response pathway EIF2AK4-EIF2A-ATF4 upon AIEC infection serves as a host defense mechanism to induce a functional autophagy, independently of mTOR, to control AIEC intracellular replication and to inhibit AIEC-induced inflammation1. Given that most of the current strategies based on modulating autophagy by targeting mTOR can have undesirable effects, targeting the EIF2AK4-EIF2A-ATF4 pathway could be a promising strategy to inhibit specifically AIEC colonization and inflammation. While host cells induce a functional autophagy as a defense mechanism to control AIEC replication, AIEC can subvert autophagy by up-regulating the levels of miR-30c and miR-130a in IECs, thus inhibiting levels of two key autophagy-related proteins ATG5 and ATG16L1. AIEC also inhibit autophagy by impairing host SUMOylation, a eukaryotic-reversible post-translational modification, in which SUMO, an ubiquitin-like polypeptide, is covalently linked to target proteins. Thus, we demonstrated the AIEC-induced impaired autophagy via the modulation of host miRNAs or host SUMOylation consequently leads to increased AIEC intracellular replication and AIEC-induced inflammation. We also showed a role for autophagy in the control of gut microbiota composition and host susceptibility to AIEC infection using genetically manipulated mouse models with a defect in autophagy. This was accompanied with increased AIEC colonization in the gut and enhanced intestinal inflammation. Of interest, upon AIEC infection, IECs and macrophages secrete an increased amount of exosomes, which are extracellular vesicles of 30 to 100 nm playing a role in cell-to-cell communication. Furthermore, the exosomes secreted by AIEC-infected cells can increase pro-inflammatory cytokine production and AIEC replication in exosome-receiving cells. Of interest, exosomes secreted by AIEC-infected IECs inhibit autophagy in exosome-receiving IECs. Mechanistically, this is mediated miR-30c and miR-130a, which are transferred via exosomes from donner cells to recipient cells, in which they directly target and inhibit expression of ATG5 and ATG16L1, respectively (unpublished data). This consequently leads to impaired autophagy response and increased intracellular replication of AIEC in cells that receive exosomes from AIEC-infected cells. These data show that exosomes are an important player in cell-to-cell communication during AIEC infection, which can carry and transfer specific miRNAs, leading to autophagy inhibition and favoring AIEC colonization. Altogether, our researches help to understand better the mechanism underlying the interaction between the host and AIEC strains. In the future, this work could contribute to the development of a personalized therapeutic strategy based on autophagy modulation for patients with abnormal AIEC colonization.

With a PhD degree in 2006 at University of Aix-Marseille III, France and a postdoc training at Department of Medicine, Emory University, USA (2006-2011), H. Nguyen has obtained a tenured position as an assistant professor at the M2iSH (Microbe, intestine, inflammation and Susceptibility of  the Host),  UMR1071 Inserm, University of Clermont Auvergne since 2012. H. Nguyen has been deeply working on the molecular and cellular mechanisms involved in the etiology of intestinal diseases such as inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Her current researches focus on the infectious etiology of these diseases, and in particular on the interaction between the host and the pathogens involved in these diseases.

  • Louisiana State University, USA
  • Title:Aluminum-Stimulated Production of Lipopolysaccharide (LPS) from the Human Gastrointestinal (GI)-Tract Microbiome-Resident Bacteroides Fragilis
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Gram-negative obligate anaerobic bacteria of the human GI-tract-microbiome and their immunogenic secretory products have significant potential to serve as a dynamic, life-long source of extremely potent pro-inflammatory enterotoxigenic compounds highly toxic to the central nervous system (CNS). These microbes and their secreted products: (i) are capable of generating a broad-spectrum of highly neurotoxic, pro-inflammatory and potentially pathogenic molecules; and (ii) these include a highly immunogenic class of amphipathic surface glycolipids known as lipopolysaccharide (LPS). Bacteroides fragilis (B. fragilis), a commensal, Gram negative, non-motile, non-spore forming obligatory anaerobic bacillus, and one of the most abundant bacteria found in the human GI tract, produces a particularly pro-inflammatory and neurotoxic LPS (Bf-LPS). Bf-LPS: (i) is secreted from the B. fragilis outer membrane into the external-medium; (ii) can damage biophysiological barriers via cleavage of zonula adherens cell-cell adhesion proteins, thereby disrupting both the GI-tract barrier and the blood-brain barrier (BBB); (iii) is able to transit GI-tract barriers into the systemic circulation and cross the BBB into the human CNS; and (iv) accumulates within CNS neurons in neurodegenerative disorders such as Alzheimer’s disease (AD). This presentation will provide evidence that the incubation of B. fragilis with aluminum sulfate [Al2(SO4)3] is a potent inducer of Bf-LPS. The results suggest for the first time that the pro-inflammatory properties of aluminum may not only be propagated by aluminum itself, but by a stimulation in the production of microbiome-derived Bf-LPS and other pro-inflammatory pathogenic microbial products normally secreted from human GI-tract-resident microorganisms.

  • Zhejiang University School of Medicine, China
  • Title:Role of CD97 in Insulinoma Extracellular Vesicles Induced Differentiation of Mesenchymal Stem Cells into Islet β-like Cells
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Obtaining sufficient donor islet β-like cells is the key to islet transplantation for type 1 diabetes mellitus. Bone marrow mesenchymal stem cells (BMMSCs) are expected to be ideal sources to obtaining islet β-like cells, however the low differentiation rate is an urgent bottleneck that need to be solved. Our group demonstrate that extracellular vesicles (Evs) derived from insulinoma can differentiate BMMSCs into islet β-like cells, and exosomes (Exos), a core component of Evs, had higher differentiation rate than Evs. In addition, we show that CD97 overexpressed Exos had higher differentiation rate than that of CD97 knockdown Exos. Furthermore, we clarify that CD97 promotes differentiation of mesenchymal stem cells into islet β-like cells through MAPK/Smad/Ngn3 pathway. Taken together, we demonstrate that insulinoma Evs, especially the Exos, were able to differentiate BMMSCs into islet β-like cells, and that CD97 plays a crucial role in the differentiation process.

Chao Li (M.D. Ph.D.) is currently fellow of Department of Surgery,Second Affiliated Hospital of Zhejiang University, School of Medicine. In 2011, Dr. Li finished his bachelor training of clinical medicine at Tongji Medical College, Huazhong University of Science and Technology. From 2011 to 2016, Dr. Li received his M.D./Ph.D. education in Zhejiang University, School of Medicine, and undertook a half year visiting scholar training in the Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada. Dr. Li’s research focuses on diabetes mellitus and malignant tumors of digestive system, specialized in the treatment of diabetes mellitus using extracellular vesicles derived from mesenchymal stem cells, as well as the metastatic mechanism of pancreatic cancer.

  • Delta University for Science and Technology, Egypt
  • Title:Modulation of Wound Processing by the Effect of Roselle Extract through TGF-β Signaling Pathway
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Wound healing consists of an organized cascade of biochemical and cellular events that involve tissue repairs and regeneration. Hibiscus sabdariffa (HS) content of polyphenols may participate by its antioxidant and anti-inflammatory properties necessary for wound healing. The purpose of this study is to assess the effect of HS loaded in ointment base applied topically to rats exposed to burning compared to standard Iruxol® ointment. Methodology: to assess wound healing potency, burn injury model was employed. Rats were divided into four groups, Group I: Normal topically applied with ointment base (Control). Group II: Burned rats were left without any treatment. Group III: Burned rats applied with topical Iruxol® ointment. Group IV: Burned rats topically applied with prepared HS extract ointment. The groups were treated with respective ointments three times through 24 hours. The wound tissues were collected to detect the oxidative stress and inflammatory effect in tissues as compared to control group. Histological analysis for tissue samples also were being endorsed the results by promoting collagen formation, re-epithelialization and angiogenesis. Results implicate that HS enhances the healing potential of the skin by stimulating the levels of biomarkers required for skin regeneration through its strong antioxidant in HS ointment applied group. In addition, HS suppressed the inflammatory effect induced by burning through its down regulation of TNF-α level. Moreover, it shows that HS topical treatment significantly reduces the hypertrophic scarring by its effect against TGF-β level. Altogether, these results suggest that HS is a valuable bioactive compound to use in wound healing and may be used with Iruxol® as synergistic product to accelerate wound processing.

Rania Khalil has her experiences in molecular biology in improving the health and protection from diseases. Her papers based on expression of genes which develop new pathways for improving healthcare. She has written these papers after several trials in research, teaching and publishing. The basis is founded on comparing gene expression before and after treatment either with a drug, complementary medicine and or food supplement. This approach has different ways of focusing that may be correlated to genetically or environmentally point of view.

  • University of Silesia , Poland
  • Title:DNA Damage in Spodoptera Exigua after Multigenerational Cadmium Exposure - A Trade-off between Maintaining DNA Stability and Adaptation Requirements
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Human activity is a serious cause of huge changes in the environment and a constant reason for the emergence of new stress factors. Thus, to survive and reproduce, organisms must constantly implement a program of adaptation to continuously changing conditions. Presented here research are focused on tracking slow changes occurring in Spodoptera exigua (Lepidoptera: Noctuidae), that were caused by multigenerational exposure to sub- lethal cadmium doses. The insects received food containing cadmium at concentrations of 5, 11, 22 and 44 µg per g of dry mass of a food. The level of DNA stability was monitored by the Comet assay in subsequent generations, up to 36th generation. In the first three generations, the level of DNA damage was high, especially in the groups receiving higher doses of cadmium in the diet. In the fourth generation, a significant reduction in the level of DNA damage was observed, which could indicate that the desired stability of the genome was achieved. Surprisingly, however, in subsequent generations alternating increase and decrease of DNA stability was observed. The observed cycles of changing DNA stability were lasting longer in insects consuming food with a lower Cd content. Thus, a transient reduction in genome stability can be perceived as an opportunity to increase the number of variants which then undergo the selection. This phenomenon occurs faster if the severity of the stress factor is high, but low enough to allow the population to survive.

Professor, PhD, DSc Maria Augustyniak is working in the Institute of Biology, Biotechnology and Environmental Protection, University of Silesia in Katowice, Poland. Major scientific interests of professor Maria Augustyniak are: aging theory, stress theory and the theory of natural selection under anthropogenic pressure; ecotoxicology; assessment of DNA stability under the influence of various environmental stress factors, including nanoparticles. Results of her works are published in prestigious journals, including: Carbon, Journal of Hazardous Materials, Fish & Shellfish Immunology, Chemosphere, Environmental Research, Scientific Reports, Environmental Pollution and many others.

  • University of Silesia , Poland
  • Title:Cd-Induced Autophagy Markers in Hemocytes and Gut Cells of the Moth Spodoptera Exigua of Increased Tolerance to Cadmium.
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Autophagy is a natural process which in physiological conditions is aimed at the elimination of destroyed or malfunctioning cell parts, organelles or molecules. Also, autophagy gets induced under stressing conditions in response to, for example, infection, starvation or oxidative stress. Cadmium as the metal regarded as highly toxic induces numerous harmful effects and reactions, including DNA damage, molecule function inhibition and oxidative stress, may also induce autophagy either directly, by interaction with molecules or indirectly through generation of free radicals. However, Cd also is known as a factor, the exposure to which may, after several generations, contribute to the selection of animal strains of increased tolerance to this element. In the Institute of Biology, Biotechnology and Environmental Protection, University of Silesia in Katowice, there is an unique strain of the moth S. exigua, selected to Cd for 170 generations (18 years). The strain exhibits cellular and organismal reactions that after the period of selection, resemble the ones noted for the control strain. Also, we have strains that are intermediate referring to both Cd concentration and time of exposure. Therefore, the aim of this study was to check whether the autophagy markers differs in insects of various Cd exposure history, including also additional acute intoxication. To reach the aim, two complementary methods: ELISA (LC3 protein level) and flow cytometry were used. Autophagy induction appeared to be significant only in the highest intensity of acute exposure.

Agnieszka Babczyńska, PhD, DSc In my research work I concentrate on relations between humans, animals and environment. As an enthusiastic ecophysiologist, in my work I apply widely understood biomarkers, from molecular markers to life history parameters, if they are able to throw a new light on the tolerance, adaptation, plasticity or selection processes of animals in response to external, especially anthropogenic factors. As animal models, I usually use invertebrates, with spiders and insects as my favorites. Equally eagerly I spend my scientific time in the laboratory and in the field. I am also an academic teacher and, I often organize and take part in popularization of researches among children and adults.

  • Pharmaceutical University, Japan
  • Title:Chronic Epipharyngitis: a Missing Background of Autonomic Nervous System Disorder and Autoimmune Disease
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It has been noticed since ancient times that colds may cause all kinds of diseases. However, its underlying mechanism has not been fully elucidated so far. Located at the back of the nasal cavities, the epipharynx is a unique tissue that is vulnerable to the effects of upper respiratory tract infections and air pollution. The epipharynx is an immunologically activated site even under normal conditions, and enhanced activation of innate immunity is likely to occur in response to airborne infection. In addition, the epipharynx has abundant distribution of vagal nerve fibers. Chronic epipharyngitis is not a widely understood condition. However, because of its close link with the nervous system and immune systems, it may play an important role as a trigger for the development of autoimmune diseases and neuroendocrine disorders, including chronic fatigue syndrome and other somatic symptoms. Thus, the epipharynx-brain interaction and epipharyngitis related immunity are worth consideration in managing patients with autonomic nervous disorder and patients with autoimmune disease. Given that chronic epipharyngitis and its brain interactions are not fully understood, it is important to focus future research on this condition.

Osamu Hotta, Medical Doctor (Ph.D.-medicine), now is a Director of Hotta Osamu Clinic, Clinical professor of Tohoku Medical and Pharmaceutical University, Councilor of Japanese Society of Nephrology, and Chairman for Japanese Focal Inflammation related Disease Research Group (JFIR). Osamu Hotta is a nephrologist, got Medical Doctor’s degree (Ph.D) at Tohoku University in 1993.

  • University of Szeged ,Hungary
  • Title:The Neonatal Isoform of Sarco/Endoplasmic Reticulum Calcium ATPase 1 has a Paradox between its Structure and Function
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The neonatal splice variant of the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA1b) is expressed specifically in myotubes and developing skeletal muscle1. This pump has a functional difference from its adult isoform, SERCA1a. The SERCA1a is expressed in myofibres of fast twitch muscle and has more capacity to pump against high vesicular Ca2+ concentration than SERCA1b does2. The only structural variance – the octapeptide tail in SERCA1b instead of the C-terminal glycine of SERCA1a3 – does not seem to explain the functional difference because the C-terminal tail protrudes into the sarcoplasm, not the lumen of the sarcoplasmic reticulum where the concentration of Ca2+ is accumulated4. This paradox hints to a possible regulatory mechanism exerted by micro peptides recently found abundant in developing muscle5. A developmental effect of this possible regulation will be presented.

  • Carol Davila University of Medicine and Pharmacy,Romania
  • Title:The Frequency of HLA Alleles in the Romanian Population
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Knowledge of human leukocyte antigen (HLA) allele frequencies is essential for bone marrow and kidney donor searches. The Romanian Caucasian population is heterogeneous and information on HLA polymorphism has not been well studied. We characterized the HLA genetic profile and allele frequencies of regional populations in Romania. HLA-A, B and DRB1 alleles were examined in 8252 individuals, belonging to the four main regions of Romania. The most common alleles found in the Romanian population are: HLA-A*01, A*02, A*03, A*11, A*24; HLA-B*18, B*35, B*44, B*51 and HLA-DRB1*01, DRB1*03, DRB1*07, DRB1*11, DRB1*13, DRB1*15, DRB1*16. More than half of the alleles are non-homogeneously spread in Romania.These results provide a starting point for future analyses of genetic heterogeneity in Romania.

I have started my medical activity as a PhD fellow at the University Hospital of Wales, Cardiff, UK, working on growth factors involved in the pathogenesis of pituitary tumours. My interest centres arround transplantation immunology, cancer immunology and virology. I have concentrated my efforts on three challenging topics: immunogenetics, new biomarkers, new genes involved in early cancer diagnosis, prognosis, immune system genetics in various diseases. At present I am Editor-in-chief at Immunogenetics: Open Access Journal and professor of immunology at Carol Davila Medical and Pharmacy University, Bucharest, Romania.

  • University of Montreal, Canada
  • Title:The Dual Regulatory Roles of miR-181a in Breast Cancer
  • Time :

Breast cancer is the most common malignant tumor in females. It represents a complex heterogeneous group of tumors that display significant diversity with respect to histopathological features and therapeutic responses. Many researchers have focused on biomarkers, which will facilitate detection of breast cancer in its early stages, and microRNAs have shown immense potential for this purpose. microRNAs are a family of highly conserved noncoding single˗stranded RNA molecules of 21-25 nucleotides. microRNAs have been shown to have important roles in oncogenesis, invasion, and metastasis via epigenetic post-transcriptional gene regulation. Recent evidence indicates that the expression of miR-181a is altered in breast tumour tissues and in the serum of breast cancer patients. Some studies have demonstrated the involvement of miR-181a in the control of gene expression in breast cancer. The main thrust of this presentation is to explain the potency of miR-181a as a prognostic and/or diagnostic biomarker and to discuss the targeting therapeutics, as well as the associated challenges.

Pierre Hardy, MD, PhD is a clinical scientist, Professor of Pediatrics, Pharmacology and Physiology at the University of Montreal who has extensive experience in translational medicine regarding solid tumors, cancer biology, gene therapy and biotechnologies (application of nanomedicines in cancer therapy). He has published over 150 papers in peer-reviewed journals. Some of his recent publications include Journal of controlled release 298 (2019): 177-185; Experimental Cell Research 386 (2020): 111737.

  • University Hospital of Cologne, Germany
  • Title:Exosomal ncRNAs, Novel Frontier of Tumor Detection by Liquid Biopsies
  • Time :

Locally advanced adeno- and squamous cell carcinoma of the esophagous (EAC, ESCC) and oral squamous cell carcinoma (OSCC) result in worse prognosis upon late diagnosis. We aim to identify tumor indicating ncRNAs in serum exosomes of tumor patients for earlier non-invasive diagnosis to contribute to a better outcome.
Differential gene and protein expression comparing tumor and normal tissues identified diagnostic, response predictive and prognostic tumor markers. Transfer to liquid biopsies now seems practicable by exosomes, components of the novel communication system of living cells. In addition to protein expressing genes, non-coding (nc-) RNAs like lnc-, circ-, and mi-RNA have been recognized as regulatory active key components with high impact for cancer development. Exosomal cargo provides an imense potential for creation of diagnostic marker signatures for earlier diagnosis. We profiled exosomal miRNAs, identified 80 exosomal miRNAs differentially concentrated between 12 OSCC tumor patients and 8 healthy blood donors. miRNome analysis was performed by TaqMan miRNA arrays. Six miRNA candidates have been selected for verification by 25 OSCC patients and 22 healthy blood donors. miR-409-3p has been identified as potential diagnostic candidate, p=0.001, fold change 0.203.
As an essiential step to detect tumor-indicative differences in exosomal cargo with better sensitivity 1. we need membrane proteins on the surface of the microvesicles, discriminating tumor cell secreted „oncosomes“ from exosomes originating from normal cells, 2. we aim to separate tumor cell derived „oncosomes“ from normal cells secreted exosomes, present in large abundance in serum of tumor patients.
By whole genome gene expression arrays we detected highly overexpressed membrane proteins as diagnostic signature which will be now examined in „oncosomal“ membranes for transfer to liquid biopsies.

Ute Warnecke-Eberz, molecular- and microbiologist, obtained PhD at the Freie University of Berlin, Germany in 1990. As head of lab for antiinfectiva research at Bayer Pharmaceutical Research in Wuppertal, Germany, she develoved screening assays to find antibacterials inhibiting protein-DNA interaction. 1999 establishing the lab for molecular oncology of the General-, Visceral- and Cancer Surgery at University Hospital of Cologne, she started research on diagnostic, response predictive and prognostic tumor markers for esophageal, gastric, oral and lung cancer. Since 2017 Prof. at University Hospital of Cologne focussing on real-time quantification of gene expression, and transfer of tumor marker results to liquid biopsy format. Actually evaluating the diagnostic use of serum exosomes and exosomal non-coding RNAs.

  • University General Hospital of Patras, Greece
  • Title:Virulence Factors of Gram Positive Bacteria Related to Ocular Infections in Immunocompetent Patients
  • Time :

The ocular surface is constantly exposed to the dangers of the environment, including pathogenic bacteria. Bacterial infections of the human eye by gram positive bacteria can cause severe visual impairments. S. aureus is a major ocular pathogen as it possesses potent virulence factors in its armamentarium: fibronectin-binding protein A (FnbpA) and Fnbp B, fibrinogen binding proteins (ClfA and ClfB), iron regulated surface determinant A (IsdA), wall teichoic acid (WTA), b-defensins 2 and 3, cathelicidin, RNase 7, cytokines, chemokines, adhesion molecules, and granulopoiesis factors, alpha-toxin, phenol soluble modulins (PSM), and Panton-Valentine leukocidin (PVL), protein A (SpA), Exfoliative toxins (ETA and ETB) and toxic shock syndrome toxin (TSST), LukAB (LukGH) and PSMs, staphylocoagulase. S. pneumoniae in eye infections is most involved in keratitis, conjunctivitis, and endophthalmitis. The microorganism firstly colonizes the nasopharynx via the neuraminidases NanA, NanB, and NanC. Then, acts through hyaluronate lyase, pneumococcal capsule, autolysin, pneumolysin, zinc metalloproteinases. Streptococcus pyogenes is most involved in blepharitis and hospital acquired conjunctivitis. Its virulence factors include: cysteine proteinase, streptococcal pyrogenic erythrogenic toxin B, streptokinase, cell envelope protease, Streptococcus secreted esterase, streptolysin O and streptolysin S, M protein, endo-β-N-acetylglucosaminidase. E. faecalis is implicated in postoperative endophthalmitis cases. These strains produce a cytolysin with a large lytic subunit (CylLL) and a small lytic subunit (CylLS) and are related with poor visual outcome. Bacillus cereus can cause a rapidly destructive endophthalmitis via its peptidoglycan, flagella, hemolysins, lipases, enterotoxins, proteases, cereolysin AB, cereolysin O, and collagenase. Corynebacterium (non-diphtheriae) species: They possess pili with tissue tropism to colonize host tissues. After initial attachment additional minor pilins help anchoring, and provide proximity between the bacterial surface and the host cell plasma membrane. The arsenal of gram positive microorganisms that can cause ocular infections and the understanding of their mechanisms of action can elucidate further therapeutic targets and promote rapid treatment.

Panagiota Xaplanteri has graduated from Medical School, Patras University in 1999 and acquired the medical specialty of Biopathology (Laboratory Medicine) in 2007. She has completed her PhD in 2008 from Medical School, Patras University, Greece and her MSc in Health Care Management, Hellenic Open University in 2018. She has worked in the following positions: Senior Assistant, Department of Microbiology, University General Hospital of Patras, Greece, 2015-today, Part time Assistant Professor, School of Rehabilitation Sciences, University of Patras, Greece, 2019-today, Part time Lecturer/Assistant Professor, School of Sciences of Health and Care, Technological Educational Institute of Western Greece, Patras, 2007-2019. She has published more than 20 papers.

  • Rio de Janeiro Botanical Garden Research Institute, Brazil
  • Title:Trichomes in Mimosa(Leguminosae): Towards a Characterization and a Terminology Standardization.
  • Time :

Mimosa, one of the most species-rich genera in the Leguminosae, exhibits a high diversity of trichomes. These structures are considered crucial to the taxonomy of the genus and are commonly used to delimit infrageneric groups. The last taxonomic revision by Rupert C. Barneby, published in 1991, provided an important reference in the understanding of trichomes in Mimosa, but some terminology still needs to be clarified and standardized. The present study describes the microstructure and anatomy of trichomes in Mimosa and suggests a terminological standardization for these structures in the genus. We examined the trichomes of 62 species and the terms used to classify them were compared with previous taxonomic studies in the genus. We recognize 15 types of trichomes primarily based on the number, arrangement, and secretory activity of cells (uni- versus multicellular, uni- versus multiseriate, simple versus branched, glandular versus non-glandular). We conclude that the type of trichomes, rather than the type of indumentum, should be used for comparative analyses.
Biologist, began his academic studies at the Rio de Janeiro Botanical Garden (JBRJ) during its graduation studying taxonomy of the genus Mimosa (Leguminosae). Obtained a master’s degree in Botany at the National Museum of Brazil in 2013 with a dissertation on floristic and taxonomic studies of Mimosa in the state of Rio de Janeiro, Brazil, and a doctorate in Botany at the JBRJ in 2019 with a thesis on phylogenetic studies based on molecular data and a taxonomic revision of four series of the genus. In 2016, he held an exchange where he worked at the New York Botanical Garden on the Reflora Project in which he digitized specimens from Brazilian flora stored at the NY herbarium, while developing part of his doctoral research. In 2019, he completed a post-doctorate at JBRJ exploring the use of many phylogenetic and biogeographic tools. Lucas worked as a biology teacher in elementary and high school for six years. He also worked as a consultant in floristic surveys, forest inventories and botanical identification and, currently, is a professor of Botany, Forensic Botany and Brazilian Environmental Law in a preparatory course for application processes of government jobs, and in a specialization course (“Post-graduation lato sensu”). Since March 2020, he has worked at National Center for Flora Conservation/JBRJ assessing endangered species. His interest in trichomes arose from the need to understand the morphological diversity of Mimosa.

  • Umm-Al-Qura University, Saudi Arabia
  • Title:New Records of Indigofera CordifoliaHeyne ex Roth. (Fabales: Fabaceae) in Saudi Arabia based on Morphological and Molecular Evidence
  • Time :

Indigofera cordifolia Heyne ex Roth. so far is reported only in the Arabian Peninsula from Oman. A recent field expedition in the Farasan Archipelago, Saudi Arabia, Red Sea, resulted in documentation of this species in Dumsuk Island. Morphological examination and molecular identification based on the nuclear ribosomal DNA internal transcribed spacer region of this plant species was investigated in this study. The result show that the internal transcribed spacer had high species-level discrimination efficiency for the identification of Indigofera cordifolia that may provide help in authentic identification and management process of this rare and nationally endangered species.

  • King George’s Medical University, India
  • Title:Differential Expression Profiling of Transcripts of IDH1, CEA, Cyfra21-1, and TPA in Stage IIIa Non-Small Cell Lung Cancer (NSCLC) of Smokers and Non-Smokers Cases with Air Quality Index.
  • Time :

Smoking tobacco is the major hazard for lung cancer in Indian subcontinent especially men, compare to
woman where, other important risk factors such as air pollutions are responsible. So, the aim of the study
is to compare chronic smokers (CS) and non-smokers living in areas with air quality categorized as poor
(AQI 201-300) or moderate (AQI 101-200). We measured the expression of non-small cell lung cancer
(NSCLC) biomarkers. IDH1, CEA, Cyfra21-1, and TPA through quantitative Real-Time PCR (qRT-PCR)
and compared the levels of upregulation of the transcripts in stage IIIa NSCLC over control benign tissues
among the smoking and AQI settings. Though the all biomarkers were significantly up-regulated in tumor
tissues compared to control benign tissues, the fold change increase of IDH1 and CEA was highest in CSpoor/moderate AQI, followed by non-smokers-poor AQI and non-smokers moderate AQI. This indicates
the aggressiveness and poor prognosis in CS living in either poor or moderate AQI areas. The level of
Cyfra21-1 was lower in in the CS groups in comparison to non-smokers in the poor AQI area. This suggest
higher Lung Squamous cell carcinoma histology in non-smokers living areas with poor AQI. Hence, we
conclude that poor air quality can be as injurious for lung cancers as chronic smoking. We also observed
pathogenic mutation KRAS p.A59T mutation comparing with CS and non-smokers under poor/moderate
AQI identified ~40% cases in all three groups suggest association with poor/moderate AQI. Additionally,
EGFR exon 20 insertion mutations in CS under poor/moderate AQI showed association with both
chronicity of smoking and poor/moderate AQI representing primary resistance to Tyrosine Kinase
Inhibitors. Hence, we conclude that poor and moderate AQI are also injurious as CS.
She has been working to understand the specific transcriptomics-based subtyping of adult and pediatric
tumors. She has received various fellowships from Indian Government funding agencies. She has various
publications in peer reviewed journals as well has been a participant of Halifax project which wrote series of reviews (13) in Seminars of Cancer Biology and Carcinogenesis.

  • University of Debrecen, Hungary
  • Title:MSC-like Cells Increase the Ability of Monocyte-Derived Dendritic Cells to Polarize IL17/IL-10-Producing T Cells via CTLA-4.
  • Time :

The final manifestation of immune responses is a result of a complex interaction of phenotypically and functionally different cell populations. Mesenchymal stromal cell-like (MSCl) cells are considered to be an eligible cell line to model the immunomodulatory behavior of mesenchymal stromal cells (MSCs) in vitro. One possible target of MSC-mediated regulation is the population of dendritic cells playing a determining role in shaping the outcome of effector cell responses. However, it is still uncovered how monocyte-derived dendritic cell (moDC) populations drive the polarization of helper T cells (Th) in the presence of MSCI-conditioned medium (MSCI-CM) or MSCI cells.
We induced the differentiation of moDCs in co-cultured with MSCI cells or in the presence of MSCI-CM, IL-4, and GM-CSF. MoDCs were characterized by flow cytometry while their cytokine production was measured by Human XL Cytokine Array Kit or ELISA. The polarization of T cell response was monitored by ELISPOT and flow cytometry.
Here, the effects of MSCl cells on the in vitro differentiation of human monocytes into DCs were investigated. MSCl cells promote the differentiation of CD14, DC-SIGN, CD86, MHC- II, and CTLA-4 expressing monocyte-derived cells partially via all-trans retinoic acid production (ATRA) functioning as a ligand of RARa, a key nuclear receptor in DC development. The presence of MSCI cells or MSCI-CM during the moDC differentiation resulted in the altered secretion of a wide array of inflammatory and immunsuppressive cytokines as well. These semi-matured DCs exhibit an ability to activate allogeneic, naive T cells and polarize them into IL-10 + IL-17 + double-positive T helper cells in a CTLA-4- dependent manner.
Thus, these data outline a novel mechanism mediated by MSCI cells, which drives moDC differentiation to a regulatory phenotype. Additionally, mapping the molecular mechanisms of MSC-mediated indirect modulation of DC differentiation may help to expand MSCs’ clinical application in cell-free therapies.
I started my studies at the University of Debrecen. I was graduated with a Bachelor of Science Degree in Biology and a Master’s Molecular biologist Degree in Immunology, Cell- and Microbiology. I advanced my Doctorate studies at the doctoral school of Molecular Cell- and Immunobiology. I worked as a junior research fellow for the Hungarian Academy of Sciences. I am currently working as a researcher and tutor in the position of a lecturer assistant at the Department of Immunology. Our research group focuses on the dendritic cell (DC) biology, more precisely, the differentiation process of dendritic cells or macrophages from monocytes.
A great target to examine the fine-tuned synergy of DCs with other immunomodulatory cells is the mesenchymal stem/stromal cells (MSC). We attempted to reveal the complex interactions between the DCs and MSCs, which could be crucial for understanding the molecular mechanisms in the pathogeneses of immune-related diseases.

  • Department of Obstetrics and Gynecology, Greece
  • Title:Fetal Heterozygosity for Both Hb G-Hsi-Tsou and Beta Thalassemia: A case report
  • Time :

This case report describes a fetus with compound heterozygosity for Hb G-Hsi-Tsou and beta thalassemia, diagnosed in a healthy pregnancy. To the best of our knowledge, this is the first documented case of compound heterozygosity and the woman is the second known case of heterozygosity for Hb G-Hsi-Tsou. A 34-year-old woman during her first pregnancy underwent routine early pregnancy screening and several tests were performed. All tests were normal, with the exception of hemoglobin electrophoresis, which revealed heterozygosity for Hb G-Hsi-Tsou. Hemoglobin G-Hsi-Tsou constitutes a hemoglobin variant with a structural abnormality of the beta chain, first described in 1972, but since then no other cases have been reported. After finding out that her husband was heterozygous for beta thalassemia, chorionic villus sampling revealed the embryo’s heterozygosity for both Hb G-Hsi-Tsou and beta thalassemia. Due to lack of scientific data, the couple decided to end the pregnancy. It was not possible to determine whether the fetus would present serious deficiencies in hematopoiesis, as Hb G-Hsi-Tsou is a variant which is not yet fully understood. What made this case even more complex was the simultaneous presence of the beta thalassemia allele.
MD Maria Androulaki graduated from the Department of Medicine, University of Patras, Greece, in 2019. She is currently in her first year of Obstetrics and Gynecology residency at General Hospital of Messinia, Kalamata, Greece. During her medical studies, she completed clinical internships at the Department of General Surgery at Zagazig University Hospital in Egypt and at the Department of General Surgery, Antoine-Béclère Hospital in Paris, France. Her main domain of interest is maternal-fetal medicine.

  • Federal University of Sao Paulo, Brazil
  • Title:Syndecan-4 as a Regulator for Anoikis Resistance
  • Time :

Anoikis is a programmed cell death that occurs when cells lose their attachment to the extracellular matrix (ECM). Cell adhesion plays an important role in neoplastic transformation. Tumors produce several molecules that facilitate their proliferation, invasion and maintenance, especially proteoglycans. The syndecan-4 (SDC4), a heparan sulfate proteoglycan, can act as a co-receptor of growth factors and proteins of the extracellular matrix (ECM) by increasing the affinity of adhesion molecules to their specific receptors. It participates together with integrins and FAK (focal adhesion kinase) in cell adhesion at focal contacts connecting the ECM to the cytoskeleton. Changes in SDC4 expression have been observed in tumor cells, indicating its involvement in cancer. Our previous works demonstrated that acquisition of anoikis resistance by blocking adhesion to the substrate up-regulates syndecan-4 expression in endothelial cells. So, we decided to further study the specific roles of SDC4 in transformed phenotype of anoikis resistant endothelial cells by specific silencing of SDC4 using micro RNA interference (miR RNAi). Our results indicated that downregulation of SDC4 expression reverses the transformed phenotype of anoikis resistant endothelial cells. A better understanding of the mechanisms underlying anoikis resistance and syndecan-4 expression may provide insight into the biology of cancer and identify novel therapeutic targets for prevention of metastasis formation.
Carla Cristina Lopes, PhD is a Professor of Cell Biology at the Universidade Federal de São Paulo, Brazil. Her major scientific interests are: proteoglycans, cancer, anoikis, metastasis, extracellular matrix and cell signaling. Results of her works are published in prestigious journals, including: Matrix Biology, Apoptosis, International Journal of Biochemistry & Cell Biology, Journal of Colloid and Interface Science, Journal of Cellular Biochemistry, Biochimica et Biophysica Acta, Plos One and others. In addition, she also has four chapters published in the book “Insights into Carbohydrate Structure and Biological Function”.

  • University of Cambridge, United Kingdom
  • Title:Use of Nasoil® via Intranasal to Control the Harmful Effects of Covid-19 and Nwe Results.
  • Time :

The virus that caused the COVID 19 pandemic spread globally with an increase in deadly infections
in most countries, COVID-19 is caused by SARS-coronavirus-2 (SARS-CoV-2), which belongs to the
coronavirus family and is related to Severe Acute Respiratory Syndrome (SARS) andMiddle East
Respiratory Syndrome (MERS) virus. Structurally, SARS-CoV-2 is a virus wrapped with a positivesense single-stranded RNA genome. Proteins on the surface of the virion are responsible for
compromising the angiotensin-converting enzyme 2 (ACE2) receptor toenter susceptible host cells;
the initial infection is predominantly directed at the epithelial cells of the lungs and throat. Spray
microdroplets are thought to be the primary mode of viral transmission.
Patients hospitalized with severe or critical infections are treated with a selection of antiviral
agents (e.g. oseltamivir, lopinavir, ritonavir, remdesivir), combinations of antibiotics and/or
glucocorticoids depending on the clinical condition of patients, in addition to assisted ventilation
when breathing capacity is compromised [8–10]. With the current magnitude of contagious
infections and associated deaths caused by COVID-19, there is an urgency to employ additional
strategies to find treatment options capable of reducing deaths. Although there are encouraging
results with some therapies, there is still a need for other strategies, particularly specific
approaches such as nutritional inter- vention, inmunoenhancer, coronavirus-specific treatments
such as coronavirus protease inhibitors, etc. (trials are currently being con- ducted around the
world) [11,12].
Patients with COVID-19 develop clinical manifestations of high fever, cough, myalgia, dyspnoea with
or without diarrhea and pneu- monia, these manifestations are among the first recognized, every
day new symptoms are put associated with COVID-19 virus, but usually patients have
gastrointestinal problems such as nausea, vomiting, diar- rhea, abdominal pain, in addition to
shortness of breath, headache, sorethroat, colds, breathing problems, myalgia, nasal congestion
and inflammation of the mucous membranes that cover the inside of the sinuses and nasal
discharge, also in some cases occur injuries to the central nervous system.
The research focuses on the treatment of the symptoms of diseases related to the modification of
structural and functional proteins such as those that make up connective tissue, some of the
symptoms that these extracts mitigate are related to respiratory, cardiac, and metabolic diseases. ,
infectious, allergic and genetic.
The development provides a remedy and process for the activation of cellular molecules, mainly
proteins to reactivate their molecular activity, the active principles being a product that combines
refined plant extracts, as well as the solvents that balance these extracts.
The present invention is specifically directed to a pharmaceutical composition for the treatment of
symptoms produced in particular cases in diseases caused by damage to endothelial cells, such as
those caused by the SARS-CoV-2 virus, and other diseases where the diseases are affected. proteins
that make up endothelial cells, through a concentration of a product that combines fractionated
plant extracts as well as the solvents that balance these extracts; this to modify proteins and avoid
extreme damage to endothelial cells at a concentration that is effective in decreasing symptoms
present in a patient
The present development is also directed to a method for the treatment in humans suffering from
the side effects produced by vaccines caused to control the SARS-CoV-2 virus using a product that
combines plant extracts, as well as the solvents that balance these extracts, which comprises the
administration to humans effective doses of the composition of said product.
The present development is also aimed at a process of regeneration of lung tissue damaged by the
SARS-CoV-2 virus in humans, which comprises the administration to humans of the effective dose
of the product that combines plant extracts, as well as the solvents that balance these extracts, at a
concentration of the product that is effective for the regeneration of lung tissue damaged by the
SARS-CoV-2 virus. It also addresses a process to protect normal cells from the cytopathic effects of
viruses, which comprises administering effective doses to humans as well as the solvents that
balance these extracts, at a concentration of the product that is effective to protect against the
effects. cytopathic viruses.
Testing with Nasoil® began on April 20, 2020, and these observa- tions were completed on July 15,
2020. The effect of Nasoil® was studied in a total of 600 individuals of which 348 were men and 252
women, the average age was 44.27 years, with ages ranging from 20 to 78 years
The study population was divided into 6 (six) groups both by their conditions and the way in which
they evaluate their health condition, being people for preventive application, as well as co-adjuvant
to regain health, the preventive application has been carried out with people of nursing areas,
treating doctors from the COVID 19 area, people who cared at home for patients sick with SARS
CoV2 and people with regular to low exposure to infection; Of this population, 100% of the people
who were applied preventively maintained their health and did not manifest symptoms of any kind
in this regard, while 100% of the population that was applied as a co-adjuvant recovered their
health. In subsequent follow-up, with an applied population of approximately 15,000 people, there
is a record that 99.85% of the people have not manifested symptoms or complications with the
infection; 0.15% were positive and 100% of them recovered their normal condition in the short
term; While in treatment of positive people 99.87% recovered their health while 0.13% died, these
people being the ones who began to apply the present development being at level 6 of severity
(according to the scale of the Royal College London).
Regarding a pre-clinical analysis in conjoint application with various preventive vaccines to SARS
CoV2, it was found that the control group manifested in 79.62% some kind of side effect such as
fatigue, dizziness, weakness, headache among others, while the People who applied Nasoil Vir1 at
the same time as being vaccinated, 100% said they had no side effects, except for pain in the arm
due to the penetration of the needle, in addition, a better immune response was found in people who received the most Nasoil vaccine Vir1 measuring the formation of antibodies in the time after
the application of said vaccine.
Carlos Cuevas leads a small independent research group, in the area of research he has been
awarded by the INIFAP system in Mexico for research aimed at developing an oil fractioning system
as well as participating in research networks such as the International Network of Fruits and Flowers.
Vegetables and the Bioenergy Network, he also founds and chairs the Health Research and
Innovation Network, holds an academic doctorate from the Autonomous University of Madrid as
well as an honorary doctorate from the Mexico Chapter of the World University Cloister.
Some of the people on the research team are:
Marco Tulio Buenrostro Nava. Director of the master’s degree in protected agriculture. More than
40 published investigations on biotechnology and phytopathology issues.
Elisa Alejandra Ramírez. University merit medal. Various publications on biotechnology and health.
Blanca Isabel Mendoza Macías Basic research in biotechnology. Various publications on molecular
Raymundo René Rivas Cáceres Director of Molecular Biology at the Autonomous University of Cd
Juárez. Member of the National System of Researchers. CONACYT. Principal national researcher in
embryonic development and cell reproduction. State Prize for Science and Technology 2015

  • Karol Marcinkowski University of Medical Sciences, Poland
  • Title:Epigenetic Mechanisms in COVID-19 and their Impact on Long-Term Central Nervous System Disturbances
  • Time :

The pandemic of SARS-CoV-2 stimulates efforts and approaches to understand its global spread. Although the recent introduction of the vaccine is a crucial prophylactic step, the effective treatment for SARS-CoV-2 is still undiscovered. A deep evaluation of symptoms and clinical parameters, as well as molecular changes, is necessary to comprehend COVID-19 and propose a remedy for affected people to fight that disease.
The analysis of available clinical data and SARS-CoV-2 infection markers underlined the main pathogenic process in COVID-19 is cytokine storm and inflammation. That led us to suggest that the most important pathogenic feature of SARS-CoV-2 leading to COVID-19 is oxidative stress and cellular damage. DNA methylation is a significant epigenetic control program that modulates gene expression in a plethora of organisms. The excess of ROS triggers epigenetic machinery in the cell by damaging 5-methylcytosine, which results in total genome hypomethylation. The lowering/decreasing of 5-methylcytosine contents is the basis of many pathologies, like cancer and cardiovascular diseases. Global DNA hypomethylation is also observed during cellular senescence. Epigenetic dysregulation, immune defects, advanced biological age, and other factors increase the risk of cytokine storm and COVID-19 fatality.
Testing COVID-19 patients for total DNA methylation and oxidation, could be a step initial for follow-up MRI scans combined with a neurological examination. That suggests the epigenetic pattern of SARS-CoV2 infection in the central nervous system as the background for further and delayed pathologies. Many data have already been collected presenting its acute manifestations in the brain. However, chronic consequences are still unknown. Because brain is the top receiver of blood per cardiac output, and therefore especially prone to redox imbalance. The already detected MRI changes in COVID-19 patients include FLAIR intensity disturbances, typically found in brain tumors, neurodegenerative disorders, and neuroinflammation.
There is still a long way to go before we fully understand SARS-CoV-2 action and pathogenesis of COVID-19, but we know already that inflammation, as well as natural compounds, are elements of the equation, and natural antioxidants should be considered as promising candidates for effectively treating patients with SARS-CoV-2.
Anna-Maria Barciszewska graduated from Poznan University of Medical Sciences with MD degree in 2005. Since then she works in the Chair and Department of Neurosurgery and Neurotraumatology at PUMS, where she received PhD degree (2011) and habilitation (2020). She is a board certified neurosurgeon (2013). She has also MSc degree in chemistry (2005) and philosophy (2008) from Adam Mickiewicz University in Poznan.
In her research work she focuses on epigenetic characterization of brain tumors in the context of diagnostic markers, response to treatment and new therapies in neurooncology.

  • Mashhad University of Medical Science, Iran
  • Title:Are Mesenchymal Stem Cells able to Manage Cytokine Storm in COVID-19 Patients? A Review of Recent Studies
  • Time :

The COVID-19 disease has recently become one of the biggest challenges globally, and there is still no specific medication. Findings showed the immune system in severe COVID-19 patients loses regulatory control of pro-inflammatory cytokines, especially IL-6 production, called the “Cytokine Storm” process. This process can cause injury to vital organs,including lungs, kidneys, liver, and ultimately death if not inhibited. While many treatments have been proposed to reduce cytokine storms, but the safety and effectiveness of each of them are still in doubt. Mesenchymal stem cells (MSCs) are multipotent cells with self-renewal potential capable of suppressing overactive immune responses and leading to tissue restoration and repair. These immuno-modulatory properties of MSCs and their derivatives can improve the condition of COVID-19 patients with serious infectious symptoms caused by adaptive immune system dysfunction. Many clinical trials have been conducted in this field using various MSCs around the world. Some of these have been published and summarized in the present article, while many have not yet been completed. Based on these available data, MSCs can reduce inflammatory cytokines, increase oxygen saturation, regenerate lung tissue and improve clinical symptoms in COVID- 19 patients. The review article aims to collect available clinical data in more detail and investigate the role of MSCs in reducing cytokine storms as well as improving clinical parameters of COVID-19 patients for use in future clinical studies.
Najmeh Kaffash Farkhad is a Ph.D. student of Medical Immunology from Mashhad university of Medical Science, Mashhad, Iran. She has studied biology in previous degrees. As a researcher she studied at the Immunology and lmmunogenetic Research Center of Mashhad University of Medical Science. She gained knowledge on the issues especially in biomedical sciences, neurological diseases like ALS, stem cell research and regenerative medicine. She has published more than 20 scientific papers in peer review international journals and greatly presented her works in more than 5 national congresses. Recently, for her Ph.D. thesis, she has focused on the effects of Mesenchymal Stem Cells and their drivatives on COVID-19 disease.

  • University of Alexandria, Egypt
  • Title:Short-Term Side Effects of Sofosbuvir on the Mitochondrial Biogenesis of Young Female Rats and Prenatal Embryos.
  • Time :

Hepatitis C virus infection is endemic in Egypt with the highest prevalence rate in the world. Without treatment, most acute infections lead to chronic, followed by cirrhosis and hepatocellular carcinoma. Sofosbuvir acts like a nucleos(t)ide analogue that specifically inhibits hepatitis C virus replication. Our study aimed to explore the molecular mechanisms and the possible side effects of the therapeutic dose of sofosbuvir on mitochondrial biogenesis and functions of liver, muscle and ovary tissues of young normal female rats and explore the possible prenatal effect of Sofosbuvir on the embryos of the exposed mother. The study was conducted on female albino rats 2 months old that was classified into 2 groups. Group I (Control group): 20 healthy female rats and Group II (exposed group): 20 female rats that was supplemented with 4 mg/kg of sofosbuvir drug for 3 months. At the end of the treatment period, 10 normal and 10 exposed female rats will be sacrificed and dissected out to obtain blood, ovary, liver and muscles. Pregnancy will be induced in 10 control females and 10 exposed females by mating with healthy male rats overnight. At gestational day 17 (GD 17) pregnant control females and pregnant exposed females will be sacrificed by cervical dislocation. The embryos with their membranes and placentas will be quickly dissected out of the uterine horns. Each embryo will be dissected to obtain the fetal liver, and muscles. The reported toxicity was mediated through suppression of Peroxisome proliferator-activated receptor gamma coactivator- 1alpha (PGC-1α), mitochondria transcription factor A that impair mitochondrial biogenesis that manifested a decline in mitochondrial DNA copy number. Also, sofosbuvir suppresses the expression of DNA polymerase γ and declines the mitochondrial NADH dehydrogenase subunit-5 content that impair the mitochondrial functions. According to our results, the ovarian tissue is the most affected organ followed by the liver and placenta while muscle tissue appears to resist sofosbuvir-induced mitochondrial toxicity. In conclusion, the effects of sofosbuvir on the ovarian mitochondrial biogenesis and functions was found to not just affect the exposed females but unfortunately may have long-lasting consequences by impairing the embryonic development and transfer these mitochondrial abnormalities to next generations.
Name: Rana Hassan Mahmoud Hassan Khafaga
Mobile: (+2011)41274363 – (+2010)24273634
Nationality: Egyptian
Birth date: 4\11\1989
Marital State: Married
General Certificate of Secondary Education, Preparatory Education, Primary Education and Kinder garden: Sacred Heart School, Alexandria, Egypt, since 1995 to 2008
Graduate, Class of 2012, Alexandria University, Faculty of science, Biochemistry Department
Major: Biochemistry
Minor: Chemistry
Grade: Cumulative GPA: 3.86 out of 4, Percentage: 95.80% (first on biochemistry Department, and fifth on the whole university)
Current activity:
Professional category: Assistant lecturer at Biochemistry department at Medical Research Institute (MRI), Alexandria University, Egypt.
I am recently a student in Ph.D degree in MRI Alexandria University since February 2018
– Working on a Project accepted by STDF organization titled by: Short-term and long-term trans-generational side effects of Sofosbuvir: Experimental study on female rats, 2019.
Certificates, courses and conferences:
The Fourth international conference on new horizons in basic and applied sciences (ICNHBAS) 26 -29 july 2019, Hurghada, Egypt, oral speaker and best oral presentation.
The second international conference on biological, environmental sciences and applications, 25-28 July 2018, Hurghada, Egypt, oral speaker and best oral presentation.
The third international conference on new horizons in basic and applied sciences (ICNHBAS) August 2017, Hurghada, Egypt, oral speaker.
IELTS certificate with a score of 6.5 in 31st of December 2015.
Third workshop on molecular therapeutics and degenerative medicine from 7th to 9th of October 2015 at the faculty of pharmacy, Alexandria University.
Second workshop on molecular therapeutics and introduction to molecular biology techniques from 15th to 18th of December 2014 at the faculty of pharmacy, Alexandria University.
6th international conference and 18th annual conference (Multi-disciplinary approach in cancer management), from 23 – 26 September 2014.
Biological Fluids between Routine Laboratory, Investigations and New Modern Technology VI, 14 July 2012- 19 July 2012
First aid and injections, Aug 2011
One international publication in American journal of biomedical sciences accepted in 18/3/2020, entitled by: The Effect of Graviola Leaves Extract on the Progression of Pancreatic Cancer in Rats
Reading (Science books, Poetry, and Novels).
Adventures and traveling
Playing tennis and coach trainer in gym
Making new friendships and communicating with others of several cultures

  • Hong Kong University, Hong Kong
  • Title:Study on the Function and Regulation Mechanism of Protein Posttranslational Modifications via Chemical Biology Approaches
  • Time :

Protein posttranslational modifications (PTMs) play essential roles in the regulation of almost all biological processes, ranging from DNA replication and gene expression to metabolism. The dysregulation of proteins PTMs often leads to human diseases such as cancer and neurodegenerative diseases. Therefore, it is of great importance to reveal the biological significance of protein PTMs and their regulatory mechanisms. Benefiting from the rapid development of mass spectrometry technology, the number of known PTMs has increased rapidly. However, only a handful of protein PTMs have been extensively studied, while the cellular mechanisms and functions of many other PTMs, particularly those newly identified ones, remains poorly understood. In this talk, I will present the new strategies and discoveries on the biological significance and regulation mechanism of several novel protein PTMs.
Dr. Bao received her bachelor’s degree in Biological Science from Nankai University and then completed her PhD in the field of Chemical Biology in Hong Kong University. Her dissertation has been selected for a Springer Thesis Award and published by Springer. Dr. Bao is now a Postdoctoral Fellow in Prof. Xiang David Li’s laboratory at Hong Kong University. Her research focuses on development of chemical biological strategies to decipher the biological functions of protein post-translational modifications (PTMs) and their regulatory mechanisms.

  • University of Chicago, USA
  • Title:Modeling the Origins of Small Cell Lung Cancer from Human Embryonic Stem Cells.
  • Time :

Small cell lung cancer (SCLC) remains a major challenge in public health because of its frequency, its lethality, and the paucity of convenient models for exploring its pathogenesis and potential therapeutic vulnerabilities. Despite recent research advances, fundamental features of SCLC, especially its initiation and progression, are not fully understood. One of the main obstacles is the development of a feasible and tractable system that allows molecular events to be evaluated for their functional changes towards the hallmarks of neoplasia during lung lineage differentiation.
To understand how and why certain constellations of genetic changes drive carcinogenesis in specialized human cell lineages, we are developing cell culture models based on directed differentiation of human embryonic stem cells (hESCs). In this report, we show for the first time that up to 10 percent of lung progenitor cells derived from hESCs can be induced to form pulmonary neuroendocrine cells (PNECs), the putative normal precursors to SCLCs, by inhibition of NOTCH signaling. In such cultures, reduction of the retinoblastoma (RB) protein, the product of a tumor suppression gene commonly mutated in SCLCs, significantly expanded the number of PNECs. But reduction of TP53 protein, the product of another tumor suppressor gene uniformly mutated in SCLCs, or expression of mutant KRAS or EGFR genes, each of which is commonly found in human lung adenocarcinomas, did not induce or expand PNECs, suggesting a lineage-specific sensitivity to loss of RB function. Subcutaneous injection of PNEC-containing cultures in which expression of both RB and TP53 was blocked produced tumors resembling early stage SCLC in immunodeficient mice. Single-cell RNA profiles of PNECs were heterogeneous; when RB levels are reduced, the profiles show similarities to RNA profiles from early stage SCLC. Taken together, these findings suggest that genetic manipulation of hESC-derived pulmonary cells will enable studies of the initiation, progression, and treatment of this recalcitrant cancer.
Huanhuan Joyce Chen received her Pharm.D. degree in Pharmaceutical Sciences at Zhejiang University in China, M.S. and Ph.D. degrees in Biomedical Engineering at Cornell University. She will be enrolled as an Assistant Professor in Pritzker school of molecular engineering and the Ben May department for cancer research at The University of Chicago in May 2020, and is currently a postdoctoral fellow with Dr. Harold Varmus at Weill Cornell Medicine.
She received a number of awards including NIH Pathway to Independence Award (K99/R00), Arnold O. Beckman Postdoctoral Fellowship, National Cancer Institute Physical Sciences in Oncology Young Investigator award and National Science Foundation Graduate Research Fellowship. She has published more than 19 papers in reputed journals, including Nature Biotechnology, Nature Medicine, Nature Communication, Cell Stem Cell, Journal of Experimental Medicine, Journal of Clinical Investigation, Lab on Chip and eLife. Her research is focused on stem cell technology and tissue engineering for modeling and studying cell biology and genetic diseases.

  • Immune-Oncological Center Cologne,Germany
  • Title:Cancer Vaccines Modified by Virus Infection: Concept, Mechanism of Function and Clinical Results
  • Time :

Biological therapies such as immunotherapy and oncolytic virotherapy are physiological and well tolerated by cancer patients. The combination of cancer vaccines with oncolytic viruses is a powerful concept. Two types of autologous cancer vaccines will be described which are modified by infection with the avian Newcastle disease virus. They instruct the immune system about relevant cancer targets (tumor antigens, TAs) and contain signals for innate immunity activation. Viral molecular patterns such as S’-PPP RNA and hemagglutininneuraminidase (HN) protein initiate early inflammatory defense reactions which contribute to activation of antigen-presenting cells (APCs) and to costimulation of T cells. The concommitant stimulation of TA-specific CD4+ and CD8+ T cells occurs in T-APC clusters. These generate cancer-reactive cytotoxic T lymphocytes (CTLs) and T cell mediated long-term immunological memory. Results from pre-clinical and clinical studies will be presented.

Volker Schirrmacher is Scientific Director of Tumorimmunology at aAZK, Cologne, Germany. He finished his studies of biochemistry with a PhD in immunology. After 5 years post-doc time in Stockholm, Sweden and London, UK, he became Full Professor and Head of Division of Cellular lmmunology at the German Cancer Research Center, Heidelberg, Germany. This position was hold for 32 years until official retirement in 2008. His scientific oevre covers more than 400 peer-reviewed publications and several books. He was awarded the Aronson Price, the Meyenburg Price and the German Cancer Award.

  • Johns Hopkins University School of Medicine,USA
  • Title:Use of Contact Lenses to Optimize Optical Coherence Tomography Scans of the Optic Nerve in Open Angle Glaucoma Suspects or Patients with Open Angle Glaucoma with High Myopia
  • Time :

Patients with myopia are at increased risk for the development of glaucoma. The inability to correct for axial length on spectral domain OCT (SD-OCT) imaging translates into a lower signal strength and scan reliability in patients with high myopia. We evaluated the effectiveness of a contact lens to increase the signal strength, assess optic nerve dimensions and nerve fiber layer thickness using SD-OCT in patients with glaucoma or who are glaucoma suspects with high axial myopia.
Methods- A single-center, prospective, interventional study of patients with axial lengths over 25.5 mm with a diagnosis of glaucoma or glaucoma suspect. The optic nerve cube 200 x 200 scan using the Cirrus SD-OCT 400 was taken first without and then repeated after the placement of the contact lens. The primary outcome measure was the change in the average nerve fiber layer thickness before and after use of the contact lens. Secondary outcome measures included the change in cup volume, disc area, and rim area.
Results- Twelve patients were recruited (20 eyes) and the average axial length was 27.06 mm and the average signal strength interval increased by 1.73 (p= 0.001). With the use of a contact lens, the average nerve fiber layer thickness was significantly thicker. None of the changes in the secondary outcome measures were significant: rim area, cup volume, or disc area. Conclusions- Based on our data, the use of a contact lens statistically improved the signal strength and average nerve fiber layer thickness of the SD-OCT scan. The ability to accurately capture the perimeter of the optic disc can be limited in the setting of peripapillary atrophy, which was present in all but two subjects. Future studies with a larger number of subjects and a wider range of axial myopia to discern if contact lens correction has a greater effect on the highest axial lengths are needed.

Meghan K. Berkenstock: Dr. Berkenstock has become an emerging leader in the field of ocular immunology. As an Assistant Professor of Ophthalmology at the Wilmer Eye Institute of the Johns Hopkins School of Medicine, her research focuses on quality improvement and identifying and treating ocular side effects of oncologic immunotherapy medications.

  • USA
  • Title:Analysis of Glycosylation in Monoclonal Antibodies
  • Time :

Monoclonal antibodies (MAbs) are rapidly growing class of therapeutic molecules in biopharmaceuticals. More than 80 therapeutic antibodies have been approved by the FDA in the last 30 years for different indications ranging from oncology to autoimmune diseases to respiratory diseases and the number is increasing year by year. Most of the current therapeutic antibodies are immunoglobulin G (IgG) with glycosylation constituting around 3% of the total mass of the molecule. Understanding the impact of glycosylation and close monitoring is critical for monoclonal antibodies and fusion proteins development as therapeutic molecule. Different forms of glycan including sialic acid (NANA/NGNA), galactose, mannose and fucose influence safety, efficacy and pharmacodynamics/pharmacokinetic property (PD/PK) of the therapeutic monoclonal antibodies and fusion proteins. This presentation will highlight the influence of different glycan variants on the drug’s behaviour in the body and draw attention to commonly employed analytical techniques to analyse therapeutic molecules and determine and quantify glycan composition, structure and glycosylation site in them.

Dr Harleen Kaur has been in the pharmaceutical industry for almost 8 years and most recently led the analytics and drug product tech transfer projects for two biologics products while working at AstraZeneca, USA. Prior to this, she worked in R&D division of Fujitsu Asia Pte Ltd in Singapore where she worked on aptamer development and played an integral role in identifying and purifying aptamers against different protein targets in collaboration with National University of Singapore, Agency of Science Technology and Research Singapore, and Japanese diagnostic enterprise Sysmex. In her current role, Dr Kaur is leading a team of analytical scientists at Aurobindo Biologics and her responsibilities include the method development, method qualification and method transfer for different biosimilar products. Dr Kaur completed her PhD in chemical and biomolecular engineering department at National University of Singapore.



  • Colombiana de Trasplantes ,Colombia
  • Title:Hand-Assisted Laparoscopic Nephrectomy: Evaluation of the Learning Curve
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Background. Hand-assisted laparoscopic donor nephrectomy (HALDN) has rapidly become the best alternative to open nephrectomy for living kidney donation. As more centers continue to adopt the laparoscopic technique, the safety of the initial transplants must be ensured while ascending the learning curve (LC). This study looks to determine the safety of HALDN and to describe the results of the LC in our center.
Methods. We conducted a retrospective review of 500 HALDNs performed in our center from July 2003 to July 2017. We analyzed demographic and perioperative characteristics and complications during the first postoperative month. We divided HALDNs into 2 groups: before and after completing the LC (50 nephrectomies). For each group, we assessed operating room time, estimated blood loss, length of stay, and complication and conversion rates.
Results. A total of 500 HALDNs were performed in the study period. Of those, 454 were analyzed in the 2 groups. The median operating room time was 2 hours, length of stay was 2 days, and blood loss was 50 cc. The overall rate of complication was 6.8%. There were significant differences between the 2 groups in operating time, blood loss, and length of stay (P < .05). No differences were found in terms of complication (P 1⁄4 .42) and con- version (P 1⁄4 .28) rates.
Conclusion. There was a significant decrease in operating time, blood loss, and length of stay in patients who underwent laparoscopic donor nephrectomy by an experienced lapa- roscopist. However, no differences were found in complication and conversion rates, which suggests that improvement in surgical training can be accomplished without altering the donor safety.

  • Dept RDDM , France
  • Title:Redox Properties of Mono- and Tri-Cyclic Cyanoenones Correlated with their Efficacy as Inducers of a Cytoprotective Phase 2 Enzyme and as Protectors against Inflammation: Potency Ranking
  • Time :

Induction of the Phase 2 enzymes is a major strategy in the chemoprotection against cancer. Inducers belong to nine different chemical classes. In this contribution we found that a measure of the tendency of thirty plant phenylpropenoids and synthetic analogues to release electrons correlates linearly with their potency in inducing the activity of NAD(P)H:quinone reductase (NQO1), a prototypic Phase 2 cancer protective enzyme.  The tendency to release electrons was determined by the energy of the highest occupied molecular orbital (EHOMO), calculated by simple quantum mechanical methods. The correlations observed establish a clear conclusion: the smaller the absolute Energy of the Highest Occupied Molecular Orbital (EHOMO) of an agent, the greater its inducer potency, (i.e., the lower its oxidation potential, the stronger its electron donor property and the greater its inducer potency). The finding of this redox ranking of the inducers demonstrates that it is possible to predictively control the genetic expression of an enzymatic defense against cancer by xenobiotics via one physical parameter, their EHOMO.

  • Volgograd Research Anti-plague , Russia
  • Title:Modification of the Francis Medium for the Conversion of Histoplasma Capsulatum to the Yeast-Like Growth Phase
  • Time :

Histoplasmosis is a dangerous deep systemic mycosis that occurs in people even with preserved immune status, which can occur as respiratory distress syndrome, tuberculosis and other deseases. The importance of verification of diagnosis is associated with the vital necessity of prescribing etiotropic antimycotic therapy for patients. The causative agent of histoplasmosis is the fungus Histoplasma capsulatum which exists in two phases – the mycelial (in the external environment) and the tissue (in the macroorganism). Proof of micromycete dimorphism is the basis for laboratory diagnostics of histoplasmosis, however, there is a problem of conversion of the pathogen into the tissue (yeast) phase on nutrient media in vitro.  The Francis medium is most known for this purpose, but in our studies FT-agar, intended for the cultivation of a special whimsicality to growth conditions tularemia microbe, enriched with fermented and defibrinated blood, D-glucose, sulfur-containing amino acids and vitamins complex proved to be  significantly more effective.  The number of colony-forming units on the FT-based Frensis medium compared with Francis medium or  FT-agar  without the appropriate additives in all the observations was significantly higher (p<0,01-0,001). The results obtained allow us to recommend this environment for practical use. These studies are confirmed by a Patent (RU 2 704 278 C1).

Dr. Novitskaya I. V. has graduated from Volgograd State Medical University, Russia. For a long time, she has been working at the Volgograd research anti-plague Institute as the head of the Department and an associate Professor of the Faculty of molecular biology and genetics of the  medical University. Her research interests include Mycology, cell biology, biotechnology, diagnostics of dangerous and opportunistic infections. She is the author of more than 100 scientific papers, including Patents and Author’s certificates.


  • Alexandria University, Egypt
  • Title:The Impacts of Seasonal Variation on the Immune Status of Nile Tilapia Larvae and their Response to Different Immunostimulants Feed Additives
  • Time :

Few data are available on the thermal tolerance of Nile tilapia fish larvae in relation to their immune status and survival. The aims of this work were to evaluate the immune status of one day old Nile tilapia (Oreochromis niloticus) larval stage collected at the beginning (March), middle (August) and at the end (October) of hatching season through morphometric assessment of the larvae parameters including yolk sac diameter, body length and width as well as the expression of some immune-related genes (rag, sacs and tlr), inflammatory (il1b and il8) and stress related genes (hsp27, hsp70). Also, to compare the effect of three different immunostimulants (β-glucan, Vitamin C, and methionine /lysine amino acids mix) on the expression of the studied genes at two variant temperatures (23±1°C and 30±1°C) in experimental study for 21 days. The immune status of Nile tilapia is affected by thermal fluctuation throughout the hatching season reflected by altered yolk sac size, length, and expression of the immune and stress related genes of the larvae, the best performances was observed at the beginning of the hatching season (March). High temperature (30 oC) suppress immune and stress responses throughout downregulation of all the genes under study, mask any effects for the immunostimulants, increased mortality in fish larvae suggesting narrow thermal tolerance range for the larvae compared with the adult fish.
We recommend the use of amino acid mix as immunostimulant for Nile tilapia larvae, it reduce the mortality percentage and improve cellular response. Also the use of β- glucan should be prohibited during this developmental stage of larvae, it induced the highest mortality percentage.

I Abeer F. El-Nahas is a professor of Genetics and Genetic Engineering at the Faculty of Veterinary Medicine, Alexandria University, Egypt science 2012. I completed my practical work of Ph.D. at Hokkaido University, Japan. My research interests lie in the area of Cytogenetics, Molecular Genetics, Gene manipulation, Gene expression, Genetic Toxicology and immunogenetics. I am the Editor in Chief of Alexandria Journal of Veterinary Medicine and serving as editorial board members and reviewers of many well reputed journals.
Thirty three research students altogether awarded Master and Ph. D degrees under her direct supervision and he has over 30 publications in international peer-reviewed journals with citation over 300 times and her publication H-index is 11.
Abeer F. El-Nahas is the co-author of numerous articles published in prestigious journals, including: Fish & Shellfish Immunology, Environmental Science and Pollution Research, Gene, Basic and Clinical Pharmacology and Toxicology, Pharmaceutical Biology, Ecotoxicology and Environmental Safety, Oxidative Medicine and Cellular Longevity, and others

  • Lomonosov Moscow State University , Russia
  • Title:Antipodal Cells of the Embryo Sac of Wheat as a Unique Object to Study Plant Polytene Chromosomes
  • Time :

Polytene chromosomes are interphase chromosomes consist of homologous chromatids, which are amplified through consecutive cycles of endoreduplication and conjugate together. Polytene chromosomes are formed in the nuclei of cells that require intense synthesis of substances in highly specialized tissues.
Antipodal cells of embryo sac of wheat is an example of plant cells with polytene chromosomes. Antipodal complex is located in the ovule between the nucellus and endosperm. Antipodal cells form a complex consisting of three cell layers – basal, which contacts with the conductive tissues, middle and apical, which contacts with the endosperm. After double fertilization antipodal cells produce substances necessary for the emerging endosperm coenocyte. Antipodal cells belong to the tissues that perform trophic and barrier functions between the maternal organism and the tissues formed after fertilization. So they play key role in development of endosperm and moreover are crucial for formation of endosperm in cultivated cereals, which are food for all the humanity.
The aim of our work was to study the morphology of the nuclei and giant polytene chromosomes of antipodal cells. The work was performed on total specimens of embryo sacs isolated from fixed wheat ovules. We used methods of light microscopy and transmission electron microscopy.
We measured DNA content in the nuclei of the antipodal cells and found that nuclear DNA content varies in the cells of the complex. The basal layer cells contain less DNA than apical layer cells. During the differentiation DNA content of nuclei increases.
Structure of antipodal polytene chromosome differ from structure of animal polytene chromosomes. Animal polytene chromosomes have disks and interdisks as a result of conjugation of chromatids along the entire length of the polytene chromosome. In regions of polytene chromosomes with the intensive synthesis of RNA, decondensation of chromatin occurs and puffs are formed. On the contrary antipodal cells are characterized by giant chromosomes in the form of bundles of threads and conjugation is found only in centromere regions. At the initial stages of the differentiation nuclei of antipodals have approximately the same size and nonsegregated polytene chromosomes. Then the nuclei of middle and apical layer cells increase in size, they have isolated individual chromosomes.
To conclude, the antipodal cells of the embryo sac in cereals are a unique object for solving the fundamental problems of cell biology and a convenient model for studying the structure of the nuclei and the stages of reforming polytene chromosomes during ontogenesis.

Tatiana Doronina is a 2nd year PhD student in Lomonosov Moscow State University, Biology Faculty in Russia at the Department of Cell Biology and Histology. The field of interest is plant cell biology, polytene chromosomes and programmed cell death.
• Doronina, T. V., Chaban, I. A., & Lazareva, E. M. 2019) Structural and Functional Features of the Wheat Embryo Sac’s Antipodal Cells during Differentiation. Russian Journal of Developmental Biology, 50(4), 194-208.
• Doronina, T. V., Chaban, I. A., & Lazareva, E. M. 2019. Structural reorganization of nuclei of wheat antipodal cells during programmed cell death. Biopolymers & Cell, 35(3), 206.

  • Instituto de Cardiologa Calle, Colombia
  • Title:Type 2 Myocardial Infarction in a Patient with Acute Abdomen Due to an Incarcerated Amyand’s Hernia
  • Time :

Background: Type 2 myocardial infarction (MIT2) is characterized by higher mortality rates compared to conventional type 1 infarction according to the European Society of Cardiology (ESC) in 2018. The purpose of this case is to identify appropriate therapeutic measures. A case of an Amyand’s Hernia that produced an MIT2 is described in this work.
Case Report: A 77-year-old male was admitted to our emergency department for acute abdominal pain in the right lower quadrant associated with the presence of an ipsilateral inguinal hernia with signs of peritoneal irritation, while complaining of chest pain. A positive troponin indicated the presence of myocardial infarction. A laparotomy was performed with the finding of an incarcerated right inguinoscrotal hernia that contained the gangrenous and perforated cecal appendix (Amyand hernia type 3). The treatment consisted of surgical correction of the hernia, an appendectomy, antibiotics and support in the intensive care unit with a positive outcome. The diagnosis of Amyand hernia type 3 was established intraoperatively, and by imaging, confirming the presence of an MIT2 according to the criteria of the fourth definition of ECS infarction.
Conclusion: In the surgical environment it is strange to find patients who present with acute abdominal pain and a myocardial infarction at the same time. It is necessary for the consultant to recognize these two entities to make a correct diagnosis and provide timely treatment to reduce any possibility of patient mortality
I am Silvia Barbosa, physician at the Fundacion Cardioinfaltil in Bogota Colombia, I am part of the research group of general surgery and emergency with the aim of improving and promoting the scientific development of my country and society. We are a leading hospital in Latin America and it is through science that we can get more answers every day by sharing knowledge.
My interest is to share the complexity of the human being, how two or more

  • Jagiellonian University ,Poland
  • Title:Silencing of RIPK4 Inhibits NF-κB Activation and IL-8 Expression in TNF-α Stimulated Melanoma Cells
  • Time :

Metastatic melanoma is an aggressive skin cancer that is notoriously resistant to current cancer therapies. Studies focused on the reciprocal interactions of melanoma and immune cells demonstrated that microenvironment-derived tumour necrosis factor (TNF-α) might induce dedifferentiation of the melanoma cells. Interleukin-8 (IL-8), a chemoattractant cytokine that has been demonstrated to positively influence tumour growth through autocrine and paracrine signalling is constitutively expressed in melanoma, however, it has remained not fully understand what factors elicit its upregulation since its expression can be regulated through a variety of mechanisms.
RIPK4 (Receptor-Interacting Protein Kinase 4) is a 91.6 kDa serine-threonine kinase belonging to the RIP family responsible for keratinocytes differentiation and stimulation of proinflammatory cytokine syntheses, such as CCL5, CXCL11 and IL8. RIPK4 is also involved in the regulation of the main signalling pathways in the cell, such as Wnt, NF-κB and acts as a “linker” between the PKC and NF-κB pathways. Constitutive activation of NF-κB pathway leads to the deregulation of gene transcription including IL-8 and plays a key role in the regulation of invasive properties and treatment resistance of melanoma.
Our studies show that RIPK4 level is manifold higher in melanoma cells than in normal melanocytes. Using interference siRNA technique we diminished the level of RIPK4 in melanoma cells and found that silencing of RIPK4 decrease activation of p65 and p-IKKα/β. Thus, we studied if IL-8 expression upon stimulation with TNF-α differs between melanoma cells with diminished level of RIPK4 expression and negative control (non-specific siRNA) by qRT-PCR and ELISA. We identified that IL-8 regulation by TNF-α in melanoma cell was mediated through RIPK4 and NF-κB activation.
The study was supported by the National Science Centre Grant number 2018/31/N/NZ3/02625 and 2018/31/B/N25/01423

I’m a PhD student in the Department of Biophysics. In my research I study signalling pathways in melanoma cells, focusing on the role of RIPK4 kinase in the regulation of melanoma cell invasiveness. I’m principal investigator in project “Engagement of RIPK4 in RAF1/MEK/ERK pathway in melanoma cells” funding by National Science Centre. Moreover recently I finished my project “Involvement of RIPK4 kinase in PKC/NFκB pathway in melanoma progression”, Grant was funded by KNOW 2018/2019 to Faculty of Biochemistry, Biophysics, and Biotechnology of Jagiellonian University.
My publication:
Skalniak L, Smejda M, Cierniak A, Adamczyk A, Konieczny P, Madej E, Wolnicka-Głubisz
A. p38 but not p53 is responsible for UVA-induced MCPIP1 expression. Mech Ageing Dev. Volume 172, June 2018, Pages 96-106
1)XLV Winter School of the Faculty of Biochemistry, Biophysics and Biotechnology of the Jagiellonian University in Cracow, Zakopane, Poland, February 2018; The involvement of RIPK4 in the regulation of melanoma cell invasiveness (poster presentation)
2)IV Nationwide Biomedical Symposium Esculap, Lublin, Poland, December 2017; The receptor – interacting protein (RIP) kinase family as a new target in anticancer therapies (oral presentation)
3)17th Congress of the European Society for Photobiology, Pisa, Italy, September 2017; The role of p38/p53 in UVAinduced oxidative stress and MCPIP1 increase (author of the poster)
4)XLIV Winter School of the Faculty of Biochemistry, Biophysics and Biotechnology of the Jagiellonian University in Cracow, Zakopane, Poland, February 2017; The role of p53 in UVA- induced oxidative stress and MCPIP1 increase (poster presentation)

  • University of Tartu, Estonia
  • Title:open-source solutions for whole slide imaging: an overview and possible application.
  • Time :

Digital pathology is rapidly evolving, transforming qualitative paradigms to quantitative ones, increasing histological examination objectivity. With a compound annual growth rate of the market over 10%, scanning devices with a higher slide capacity, speed and resolution become available. Not of less importance is software, varying from free basic viewers ending with advanced machine learning algorithms promising (semi) automatic diagnosis. To a significant extent, the advantages of computer-assisted image analysis may first be experienced via open-source solutions. The session provides an overview of existing free WSI-oriented solutions and examples of possible applications in teaching, scientific research, and pathologists’ daily practice.

Pathologist, the founder of Estonian Digital Pathology Association. Co-developer of the first digital-pathology department in Estonia. Co-author of digital pathology solutions for medical and medical technician students in Estonia.

  • Buckingham Browne & Nichols School, USA
  • Title:The Application of DNA Nucleotide Footprint Plotter and Peptide Visualizer to Coronavirus
  • Time :

Direct visualization of the key features of coronavirus genomes and peptides can lead to a better understanding of this virus as well as to distinguish the mutant strains. The current study developed Java tools DNA nucleotide footprint plotter and peptide visualizer. DNA nucleotide footprint plotter makes it possible for straightforward visualization of the characteristics of viral genomes and recombination. Peptide visualizer is sensitive to changes in protein sequences and functions. The tools provide novel insights for biological studies that can contribute to breakthroughs in coronavirus diagnosis, treatment, and prevention.
I am a junior in Buckingham Browne & Nichols school in Cambridge, Massachusetts, USA. I took biology and AP JAVA. The outbreak of coronavirus made me realize the importance to write tools to explore the genome and peptide characteristics of this virus. So I developed “DNA nucleotide footprint plotter” and “Peptide Visualizer”. The tools can directly display the key features of viral genomes and peptides and make intuitive visualization of different types of virus genomes and proteins.
In my leisure time, I spend a lot of time playing and writing video games, playing violin, participating robotics club and leading a rocketry club. I also enjoy crewing and scrolling on Charles river in Boston.

  • National University of Colombia, Colombia
  • Title:Characteristics of PlasWD-40-1 and the HSP70-2/BiP/GRP78 Homolog PfHSP70-2 Proteins, their Possible Correlation, Role in Exporting Proteins Beyond its Shore
  • Time :

Globally, efforts to advance malaria control and prevention have focused on two main areas of research: (1) Finding vaccine candidates to immunize populations and prevent posterior infections, (2) Finding novel and unknown molecules and fields where remain interesting questions unsolved. The intracellular malaria parasite Plasmodium falciparum organization, particular organelles as endoplasmic reticulum and domains of the infected erythrocytes affected by changes and modifications to evading the immune response, are important basic studies. P. falciparum export virulent proteins and built a complex cell modified to transport proteins traversing three concentric membranes or cellular compartments as; plasmatic membrane of the parasite, parasitophorous vacuolar membrane, and plasmatic membrane of infected erythrocyte getting alterations for own benefit and survive. Released merozoites ending the intraerythrocytic cycle after 48 hours of the invaded cell cause symptoms of disease, physiopathology and are highly immunogenic. Our group prepared monoclonal antibodies to study the event that occurs when merozoites egress from their host, this immunogen inoculated to generate the antibodies recognizing proteins localized in the Protein export compartment (PEC). PEC is a domain of the endoplasmic reticulum that could be associated with egress merozoites. However, before studying this event, it is necessary to know the identity of proteins localized in PEC. One of the proteins localized is named Pf68kDa, which is the first resident protein of PEC, identified and is recognized by a monoclonal antibody, mAb7.
We show identification of the 68 kDa antigen of P. falciparum. Recently works identified Pf68 kDa as two proteins by different methodological strategies, and the same mAb7: the first protein identified as a homolog of HSP70/BiP/GRP78, named PfHSP70-2 by affinity chromatography and mass spectrometry, and the second protein identified, Plasmodium WD40 repeat-containing protein-1 (PlasWD40-1) identified from a cDNA expression library screened with Mab7. From the plaques analyzed, two positive clones ultimately were identified. Thus, Mab7 not only recognizes PfHSP70-2 but also recognizes a protein expressed by the cloned DNA fragment (MK618679). Now, We know more about the nature of PEC, and not much about PlasWD40 and Pf68kDa is not precisely known. It is unknown if a common epitope between PfHSP70-2 and PlasWD40-1 is a coincidence or both proteins are interacting or regulating functions to directing activities in the endoplasmic reticulum to exporting proteins to the plasmatic membrane of P. falciparum-infected erythrocytes. The target from these two proteins and common epitope or each one separately, could to proposing new possible therapeutic strategies against malaria.
Dr. Gladys Thalia Cortés obtained her Ph.D. in Biotechnology from Science Faculty at Universidad Nacional de Colombia (2020), Master Science degree at Universidad Javeriana (1995), and specialization training in immunochemistry and cellular immunology at National Institute of Health from Tokyo (Japan, 1986). Her primary field is Bacteriologist. Her studies in cell Biology of Plasmodium began with profesor Winograd E. at the Instituto Nacional de Salud (Bogotá), Wiser M., as consultor and co-investigator from Tulane University. She continued searching the cell Biology of Plasmodium at National University of Colombia (2005- ) in collaboration with Biofísica y Biología de membranas, Dr. Camacho M. at Centro Internacional de Física, Public Health Department at Faculty of Medicine. Her group published recently aspects related to, identification of antigen named Pf68 kDaPlasmodium falciparum resident protein of and specialized domain of the endoplasmic reticulum, or Plasmodium export compartment (PEC), PfHSP70-2 and (2020) and Plasmodium WD40 repeat-containing protein-1 (PlasWD40-1) identified from a cDNA expression library screened with Mab7 (2021), both proteins hypothesized as share a common epitope recognized by a same monoclonal antibody, mAb7 (doctoral thesis, 2019); besides, a study of release merozoites process from its host by photoconversion fluorescent compound to electron microscopy (2011), and characterization of proteins localized to a subcellular compartment associated with an alternate secretory pathway of the malaria parasite (2003). Currently, she is a Ph.D. researcher and professor of the Department of public health Faculty of Medicine at Universidad Nacional de Colombia.

  • Universitas Brawijaya, Indonesia
  • Title:MiR-155–5p Predictive Role to Decelerate Foam Cell Atherosclerosis through CD36, VAV3, and SOCS1 Pathway.
  • Time :

MicroRNAs (miRNAs) are noncoding RNA molecules that play a significant role in atherosclerosis pathogenesis through post-transcriptional regulation. In the present work, a bioinformatic analysis using TargetScan and miRdB databases was performed to identify the miRNAs targeting three genes involved in foam cell atherosclerosis (CD36, SOCS1, and Vav3). A total number of three hundred and sixty-seven miRNAs were recognized and only miR-155-5p was selected for further evaluation based on Venn analysis. Another objective of this study was to evaluate the biological process and regulatory network of miR-155-5p associated with foam cell atherosclerosis using DIANA, DAVID, Cytoscape, and STRING tools. Additionally, the comprehensive literature review was performed to prove the miR-155-5p function in foam cell atherosclerosis. miR-155-5p might be related with ox-LDL uptake and endocytosis in macrophage cell by targeting CD36 and Vav3 genes which was showed from the KEGG pathways hsa04979, hsa04560, hsa04810, and GO:0099632. Furthermore, miR-155-5p was also predicted to increase the cholesterol efflux from macrophage by inhibit SOCS1 expression based on KEGG pathway hsa04120. Eleven original studies were included in the review and strongly suggest the role of miR-155-5p in foam cell atherosclerosis inhibition.
Key words: miR-155-5p; foam cell; CD36; Vav3; SOCS1
Ermin Rachmawati
Lecturer in Faculty of Medicine and Health Sciences UIN Maulana Malik Ibrahim Malang, Indonesia
Doctoral student in Faculty of Medicine Universitas Brawijaya, Malang Indonesia

  • University of Zurich, Switzerland
  • Title:Myoglobin, Expressed in Brown Adipose Tissue of Mice, Regulates the Content and Activity of Mitochondria and Lipid Droplets.
  • Time :

The identification of novel physiological regulators that stimulate energy expenditure through brown adipose tissue (BAT) activity in substrate catalysis is of utmost importance to understand and treat metabolic diseases. Myoglobin (MB), known to store or transport oxygen in heart and skeletal muscles, has recently been found to bind fatty acids with physiological constants in its oxygenated form (i.e., MBO2). Here, we investigated the in vivo effect of MB expression on BAT activity. In particular, we studied mitochondrial function and lipid metabolism as essential determinants of energy expenditure in this tissue. We show in a MB-null (MBko) mouse model that MB expression in BAT impacts on the activity of brown adipocytes in a twofold manner: i) by elevating mitochondrial density plus maximal respiration capacity, and through that, by stimulating BAT oxidative metabolism along with the organelles` uncoupled respiration; and ii) by influencing the free fatty acids pool towards a palmitate-enriched composition and shifting the lipid droplet (LD) equilibrium towards higher counts of smaller droplets. These metabolic changes were accompanied by the up-regulated expression of thermogenesis markers UCP1, CIDEA, CIDEC, PGC1-α and PPAR-α in the BAT of MB wildtype (MBwt) mice. Along with the emergence of the “browning” BAT morphology, MBwt mice exhibited a leaner phenotype when compared to MBko littermates at 20 weeks of age. Our data shed novel insights into MB’s role in linking oxygen and lipid-based thermogenic metabolism. The findings suggest potential new strategies of targeting the MB pathway to treat metabolic disorders related to diminishing energy expenditure.
Thomas A. Gorr:
1982-1988:Study of Biology, Philipps-University Marburg, Marburg, Germany;
1989-1993:PhD thesis in Protein Chemistry at the Max-Planck-Institute for Biochemistry,
Martinsried, Germany;
1994:Dr. rer. nat. (PhD), Ludwig-Maximilians-University, Munich, Germany;
1994-2004:postdoctoral stay in USA: a) UT Austin TX; b) Harvard Medical School;
2005-today:Leader of independent hypoxia/metabolism research group; Univ. Zurich;
2014:Habilitation (PD) in Comparative Physiology, Vetsuisse Faculty, University Zurich.

  • University Kebangsaan Malaysia, Malaysia
  • Title:Cytotoxicity of Antimicrobial Peptides from the Skin Mucus of Anabas Testudineus on Breast Cancer Cell Lines.
  • Time :

In this study, we characterised and evaluated the anticancer activity of the antimicrobial peptides (AMP)s excreted by Anabas testudineus. To induce AMPs production, A. testudineus was exposed to heat de-activated Pseudomonas aeruginosa for 10 days. The secreted mucus was then extracted and subjected to antibacterial activity testing by disc diffusion method to confirm the fish’s AMPs production. The crude mucus was able to inhibit P. Aeruginosa, and Escherichia coli (inhibition zone were 12 ± 0.43 mm and 10 ± 0.23 mm, respectively). The crude mucus was then screened against human breast cancer cell lines MCF7 and MDA-MB-231 with IC50 of 4.27 ± 0.15 mg/ml and 4.97 ± 0.25 mg/ml, respectively. After further fractionation, identification through peptide sequencing and anticancer screening, two peptides, designated as AtMP1 and AtMP2 (23 kDa and 20 kDa respectively) has been identified to inhibit MCF7 and MDA-MB-231 cell lines. These peptides were then synthetically produced and subjected to cytotoxic assay to prove its efficacy against breast cancer cell line. The IC50 for AtMP1against MCF7 and MDA-MB-231 were 8.25 ± 0.14 μg/ml and 9.35 ± 0.25 μg/ml respectively, while IC50 for AtMP2 were 5.89 ± 0.15 μg/ml and 6.97 ± 0.25 μg/ml respectively. The peptide did not inhibit the proliferation of HS27 normal cell line. This study provided new prospects in the development of highly effective and selective cancer therapeutics based on antimicrobial peptides from animal mucus.
Dr. Mohd Shazrul Fazry graduated from The University of Queensland, Australia with a Ph.D. in Carcinogenesis. Since then, he has been working with potential local food product and natural resources to combat cancer.

  • Danish Cancer Society Research Center, Denmark
  • Title:Compromising Plasma Membrane Repair in Cancer Cells.
  • Time :

Injuries to the cell membrane of cancer cells, which are caused from invasive behavior, enhanced membrane dynamic and metabolic stress pose lethal threats to cancer cells. However, cancer cells cope by activating their plasma membrane repair system, which depends on mechanisms to remove damaged membrane by excision, internalization by endocytosis or reorganization of actin around the hole to reseal the wound. Proteins belonging to the annexin family are often found highly expressed in various cancer types and are characterized by their Ca2+-dependent binding to anionic phospholipids in the plasma membrane. Annexin family members share the ability to glue adjacent membranes together during wound healing but our recent results show that they play roles that are more specific in membrane repair by regulation of membrane excision, shedding, and induction of membrane curvature in cancer cells. Our findings open a novel avenue to target cancer cells by compromising annexin mediated plasma membrane repair. Here, novel molecular aspects of targeting the membrane repair system in cancer cells by phenothiazines, which alter plasma membrane properties and sensitize to membrane injury by inhibiting annexin-mediated repair will be presented.
Dr. Jesper Nylandsted is Group Leader at the Danish Cancer Society Research Center in Copenhagen. His work focuses on alternative death pathways and repair mechanisms in cancer cells and novel approaches to target these processes. Using biophysical methods and live cell imaging, his group has revealed fundamental processes in cell death signalling and plasma membrane repair mechanisms of cancer cells.

  • University hospital of Freiburg, Germany
  • Title:Enhanced AC133-Specific CAR T Cell Therapy Induces Durable Remission in Mice with Metastatic Small Cell Lung Cancer.
  • Time :

Metastatic small cell lung cancer (SCLC) is not curable. While SCLC is initially sensitive to chemotherapy, remissions are short-lived. The relapse is induced by chemotherapy- selected tumor stem cells, which express the AC133 epitope of the CD133 stem cell marker. We studied the effectiveness of AC133-specific CAR T cells post-chemotherapy using human primary SCLC and an orthotopic xenograft mouse model. AC133-specific CAR T cells migrated to SCLC tumor lesions, reduced the tumor burden, and prolonged survival in a humanized orthotopic SCLC model, but were not able to entirely eliminate tumors. We identified CD73 and PD-L1 as immune-escape mechanisms and combined PD-1-inhibition and CD73-inhibition with CAR T cell treatment. This triple-immunotherapy induced cures in 25% of the mice, without signs of graft-versus-host disease or bone marrow failure. AC133+ cancer stem cells and PD-L1+CD73+ myeloid cells were detectable in primary human SCLC tissues, suggesting that patients may benefit from the triple-immunotherapy. We conclude that the combination of AC133-specific CAR T cells, anti-PD-1-antibody and CD73-inhibitor specifically eliminates chemoresistant tumor stem cells, overcomes SCLC-mediated T cell inhibition, and might induce long-term complete remission in an otherwise incurable disease.
Current Position: Professor in Faculty Medical and Life Sciences University Furtwangen. Group Leader in Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center – University of Freiburg, Germany.
Research: Dr. Taromi is molecular biologist; her research is concentrated on the development of novel CAR T cell-based approaches against SCLC. Dr. Taromi is conducting preclinical studies on the mechanisms of SCLC metastasis formation, inhibitory tumor microenvironment, stem cell-based resistance and T cell infiltration of solid tumors.

  • University of Castilla-La Mancha , Spain
  • Title:The Role of DLK1, an Inhibitory Non-Canonical Ligand of NOTCH Receptors, in the Osteoblastic Differentiation of Pre-Osteoblastic MC3T3-E1 Cell Line.
  • Time :

We analyzed the role of DLK1 protein, an inhibitor of NOTCH receptors, in the osteogenic differentiation of MC3T3-E1 pre-osteoblastic cells, which lack endogenous Dlk1 expression. We have generated pools of cells stably overexpressing DLK1 protein by plasmid transfection. Dlk1 expression levels were analyzed by RT-qPCR and DLK1 protein levels by Western Blot. We performed osteogenic differentiation assays by treatment with culture medium supplemented with 10 mM β-glycerophosphate and 50 μg/ml ascorbic acid. The differentiation capacity of the DLK1-overexpressing cells was assessed by alkaline phosphatase staining and by the analysis of osteogenic differentiation markers by RT-qPCR. These assays were also performed using DAPT, a pharmacological inhibitor of NOTCH receptors. We have observed that the cells overexpressing Dlk1 showed a lower rate of osteogenic differentiation with respect to control cells, as shown by the lower degree of alkaline phosphatase staining and lower mRNA expression of some osteogenic markers, such as Alpl, Col1A1, Runx2 and Osteocalcin. The NOTCH receptor inhibitor, DAPT, also caused the decrease of both alkaline phosphatase staining and osteogenic markers in MC3T3-E1 cells treated with the osteogenic inducers. The results obtained indicate that Dlk1 overexpression or treatment with DAPT exert an inhibitory effect on the osteoblastic differentiation of MC3T3-E1 cells. This indicates that NOTCH signaling is required for osteogenesis of these cells and that DLK1 could exert its inhibitory effect on this process through inhibition of NOTCH signaling.
I graduated in Biological Sciences at the University of Salamanca, Spain. My PhD Thesis was defended in April 1997 with honors. I started my postdoctoral stage at CBER (FDA, NIH Campus, Bethesda, MD, USA), where I applied my knowledge about yeast field to the study of the interaction of the mouse membrane protein DLK1 with the NOTCH1 receptor. In October 2000, I joined the Department of Biochemistry and Molecular Biology of the Faculty of Medicine of Albacete, UCLM, Spain. Now, I am working as a Full-Time Associate Professor, and I teach the first cycle of Biochemistry and Molecular Biology in the Degrees of Medicine, Pharmacy and Biotechnology. In my research work, I have mainly continued with the study of the function and mechanism of action of NOTCH receptors and DLK proteins in cell differentiation and cell proliferation. I have published several articles in international journals, whose papers have been presented in various national and international congresses. I have co-directed 3 PhD Theses, and I actively participate in several academic committees.

  • University of Castilla-La Mancha , Spain
  • Title:High Expression Levels of DLK2 Protein in Human MDA-MB-231 Breast Cancer Cells Inhibits NOTCH1 Activation and Tumor Growth in Vivo.
  • Time :

NOTCH receptor signaling has been implicated in the development of triple-negative breast cancer tumors. DLK2 protein, a non-canonical NOTCH signaling inhibitor has previously been shown to be involved in skin cancer. In this work, we studied whether different DLK2 expression levels affected the breast cancer features of MBA-MD-231 cells. We found that higher DLK2 expression levels led to stronger NOTCH1 inhibition. Cell cycle dynamics and apoptosis were affected by DLK2 in opposite directions, depending on the levels of NOTCH1 inhibition generated by the different levels of DLK2 expression. Only a strong inhibition of NOTCH1 by DLK2 led to a decrease in cell growth. The invasive properties of these cells were also affected. Low DLK2 expression levels led to an increase in invasiveness, whereas higher DLK2 expression levels did not significantly modify MBA-MD-231’s invasive properties. These alterations were associated to changes in the expression levels of cell adhesion proteins, such as N- and E-CADHERIN. DLK2 expression levels also affected some members of other cell signaling pathways, including ERK1/2 MAPK, AKT, and rpS6 kinases. Finally, MDA-MB-231 cells expressing high DLK2 levels were unable to generate tumors in vivo in a nude mice model. Our data support an important and complex role of DLK2 protein in the control of NOTCH signaling, tumor properties and growth dynamics of triple-negative breast cancer cells.
I graduated in Pharmacy in 2000 from San Pablo CEU University (Spain). After obtaining a predoctoral fellowship, I defended my Diploma of Advanced Studies in Biochemistry and Molecular Biology at the Complutense University of Madrid and subsequently, my Doctoral Thesis on adipogenic differentiation, which obtained the highest grade, at the UCLM, Spain (2005). Within my scientific training, my stays abroad in prestigious laboratories, such as the FDA, Maryland and KMEB, Denmark, stand out. In 2008, I joined the Oncology Research Unit of the Albacete Hospital where I initiated a line of research on the study of DLK proteins in tumor processes.
Currently, I work as Assistant Professor and teach Biochemistry and Molecular Biology in the Pharmacy, Medicine and Biotechnology Degrees and I actively participate in several academic commissions (UCLM). During these years, I have directed several TFG, TFM, DEA and Doctoral Theses that have received the highest marks. I have published several articles in international journals, mainly related to the effect of DLK and NOTCH proteins in tumor growth and migration, as well as in adipogenic differentiation.

  • University of Castilla-La Mancha , Spain
  • Title:NOTCH Receptors in Osteoblastogenic Differentiation.
  • Time :

The purpose of this work is to analyse the role of NOTCH receptors on the osteoblastic differentiation of mesenchymal C3H10T1/2 cells. To reach this objective cell populations stably overexpressing each of the four NOTCH receptors were generated by transfection with a plasmid. Expression levels of Notch1-4 genes and its
target genes, Hes1 and Hey1, were assessed by RT-qPCR. The level of each NOTCH receptor in its overexpressing population was determined by Western blot. NOTCH activity was measured by luciferase assays. The osteoblastic differentiation capacity of each population was evaluated by the alkaline phosphatase staining method of induced cell cultures and the measurement of the expression levels of osteogenic differentiation markers in RNA samples obtained from differentiation assays.
The overexpression of a single NOTCH receptor produces an increase in the global NOTCH activity and modifies the expression of the other Notch and their target genes, Hes1 and Hey1. The generated transfectants showed different levels of osteogenic differentiation in in vitro assays. Alkaline phosphatase staining was more intense in cells overexpressing NOTCH3 or NOTCH2 and less intense in cells overexpressing NOTCH1 or NOTCH4. Populations overexpressing NOTCH1, NOTCH2 or NOTCH3 exhibit an increase in mRNA expression of markers compared with the control. Cells overexpressing NOTCH4 only showed a significative increase in Alpl marker expression.
Results indicate that the expression of Notch, Hes1 and Hey1 is interrelated and that the overexpression of the NOTCH1-3 receptors seems to have an inducing effect on the osteoblastic differentiation of C3H10T1/2 cells, while NOTCH4 overexpressing cells does not seem to modify the osteoblastic process.
I pursued my bachelor’s degree in biotechnology in the Technical University of Madrid (2016/2020). During that period, I worked in plant molecular biology in the Centre of Plants’ Biotechnology and Genomics (CBGP). During 2020/2021 academic course I did my Maestry in Experimental Biomedicine. Since September 2020 I have been researching in cell differentiation in the Biochemistry Lab of the Medicine Faculty (UCLM).

  • University of Castilla-La Mancha , Spain
  • Title:Dlk Proteins Modulate The Osteogenic Differentiation of C3h10t1/2 Mesenchymal Cells
  • Time :

DLK1 and DLK2 are transmembrane proteins known to be involved in the regulation of cell differentiation processes, such as adipogenesis, through the negative modulation of NOTCH signaling. Here, we examinate their possible roles in the osteogenic differentiation of mesenchymal C3H10T1/2 cells. We generated stable transfectants with plasmids that allow overexpress or diminish the expression of DLK1 or DLK2 proteins. Expression levels of these proteins were confirmed by using RT-qPCR and Western blot assays, and the activation of global NOTCH signaling was assessed by luciferase assays. We performed osteogenesis assays for 21 days and analyzed the mRNA expression of osteogenic markers, by using RT- qPCR assays, and the osteogenic capacity, by using the alkaline phosphatase staining method. Finally, we measured the phosphorylation levels of ERK1/2 MAPK, an essential kinase in osteogenesis, by using Western blot. Overexpression of DLK1, which inhibits NOTCH signaling, in C3H10T1/2 cells diminished the expression of osteogenic markers, alkaline phosphatase staining levels and ERK1/2 MAPK phosphorylation levels. Similarly, treatment with DAPT, a pharmacological inhibitor of NOTCH signaling, inhibited osteogenic differentiation. In contrast, overexpression of DLK2, or a lower expression of DLK1, promoted osteogenic differentiation by increasing the expression levels of osteogenic markers, alkaline phosphatase staining levels and ERK1/2 MAPK phosphorylation levels. On the other hand, low DLK2 expression did not bring out significant changes in the osteogenic process of these cells. Given these results, we concluded that DLK1 inhibits osteogenic differentiation of C3H10T1/2 cells, similarly to the NOTCH signaling inhibitor, DAPT, and inhibits ERK1/2 phosphorylation, whereas DLK2 enhances osteogenesis and activates ERK1/2 MAPK phosphorylation.
I studied a degree in Pharmacy at University of Castilla-La Mancha, Spain. During those years, I got the chance to join several research teams and learn different laboratory skills thanks to the Research Initiation Program developed by the Faculty of Pharmacy. In 2016, when I finished my degree, I became a PhD student, got a grant and joined the research team of Biochemistry and Molecular Biology at the Faculty of Medicine, where I did my PhD Thesis, with honors, about the role of NOTCH receptors and DLK proteins in the osteogenic differentiation of C3H10T1/2 cells. These results have been presented in various national congresses and published in some articles in international journals. Now, I go on studying the role of these proteins in different processes related with cell proliferation and differentiation, such as adipogenesis.

  • Hokkaido University, Japan
  • Title:Prostaglandins in Teleost Ovulation: A Review of the Roles with a view to Comparison with Prostaglandins in Mammalian Ovulation.
  • Time :

Ovulation, which is induced by the ovulatory luteinizing hormone (LH) surge in vertebrates, is a dynamic process that results in a discharge of one or more fertilizable oocytes from the ovarian follicle into the ovarian cavity or into the abdominal cavity. Follicle rupture is a core event of the ovulatory process and has been the subject of intensive investigation. Prostaglandins are well known to be central regulators of vertebrate ovulation. Studies addressing the role of prostaglandins in mammalian ovulation have established that they are involved in the processes of oocyte maturation and cumulus oocyte complex expansion. In contrast, despite the first indication of the role of prostaglandins in teleost ovulation appearing 40 years ago, the mechanistic background of their role has long been unknown. However, studies conducted on the teleost medaka over the past decade have provided valuable information. Emerging evidence indicates a critical role of prostaglandin E2 and its receptor subtype Ptger4b in the process of follicle rupture. In addition, our studies have revealed that activation of the melatonin/melatonin receptor system in the ovulating follicle is required for the prostaglandin E2-mediated follicle rupture process. In this talk, we summarize studies addressing the role of prostaglandins in teleost ovulation and describe recent advances. To help understand differences from and similarities to ovulation in mammalian species, the findings on the roles of prostaglandins in mammalian ovulation are discussed in parallel.
*Takayuki Takahashi, Ph.D., Emeritus Professor of Hokkaido University, Japan
1979 Ph.D. in Zoology (Hokkaido University)
1980-1986 Research Associate, Protein Studies Lab at Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
1987-1993 Assistant Professor, Faculty of Science, University of Tokyo, Japan
1993-2016 Professor, Faculty of Science, Hokkaido University, Japan
2016-2019 Research Professor, Hokkaido University, Japan
Research interests
My research activities are in the field of reproductive biology of vertebrates including fish. In particular, my laboratory has been closely associated with ovulation studies using a teleost medaka by cellular and molecular biological approaches. Our final goal is to get insights into the evolutional aspect of ovulation in the animal kingdom.
We were the first to report that, using the teleost medaka, (i) MMPs and plasminogen activator/plasmin are involved in follicle rupture during ovulation (PNAS, 2005; Biol. Reprod., 2012, 2015). In addition, our studies showed that (ii) many ovulation-related-genes are induced by the surge of LH at ovulation (PLoS ONE, 2013; Biol. Reprod., 2014; MCE, 2017), (iii) activation of the prostaglandin E2 and the receptor system is required for follicle rupture (MCE, 2011, 2012, 2017; Biol. Reprod., 2016), and (iv) follicle rupture during ovulation is the process which proceeds under precise endocrine control (MCE, 2017; Reproduction, 2019; cells, 2019).
In 2010, Prize from the Zoological Society of Japan
“Discovery of ovulatory proteases and elucidation of follicle rupture mechanism in teleost medaka”