International
Translational and Regenerative Medicine Conference

April 25-27, 2018 | Rome, Italy

Program Schedule

  • Keynote Speaker

    Time:
    09:30-10:10

    Title

    Title: Fetal Cells Role in Combating Adult Anemia: A Study of Cord Blood Transfusion in Adults from 1999 till Date

    Niranjan Bhattacharya
    Calcutta School of Tropical Medicine, India
    Biography
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    Biography

    Niranjan Bhattacharya
    Calcutta School of Tropical Medicine, India

    Dr. Niranjan Bhattacharya holds a MD in Obstetrics and Gynaecology, MS in General Surgery and a DSC in Developmental Immunology. His principal specializations are cell and tissue therapy. Has presented Invited lectures in several international universities and institutions. Has published widely in international and national journals on cord blood and regenerative medicine; is the co-editor of five books on the subject published by Springer. Currently, Chair Professor and Head of the Department, Regenerative Medicine and Translational Science, and Director General, first Public Cord Blood Bank in India, Calcutta School of Tropical Medicine, Kolkata. Cited among top five global cord blood influencers by BioInformant.



    Abstract
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    Abstract

    Niranjan Bhattacharya
    Calcutta School of Tropical Medicine, India

    There are about 100 million births in the world annually at a conservative estimate. In India, there are over 20 million births per annum, which means that over 20 million placentas are discarded every year as waste. One of the products of the placenta is cord blood; it has immense potentials. An estimated 8,785,000 Litres of cord blood is produced globally per year if an average of 84-90 ml/placenta collection is assumed. Our group of medical scientists and clinicians transfused ABO screened and HLA matched randomized fetal blood in cases of anemia resulting from malaria, diabetes, thalassemia, leprosy, rheumatoid arthritis, tuberculosis, malignancy, AIDS, and found it not only to be safe but perhaps providing additional benefits that need further study. In parts of the world where research is ongoing, a microscopic section of cord blood’s mononuclear cells (0.01% nucleated cells) is used for transplantation purposes, while the rest, i.e., 99.99% is discarded. But the discarded part has many potential uses. Cord blood is free from infection, hypoantigenic in nature, has an altered metabolic profile, is enriched with growth factors and cytokine filled plasma and has a potentially higher oxygen carrying capacity than adult blood The blood volume of a fetus at term is around 80-85 ml/kg. The placental vessel at term contains approximately 150 ml of cord blood. Cord blood contains three types of hemoglobin, HbF (major fraction), HbA (15-40%) and HbA2 (trace amounts). HbF, which is the major component, has a greater oxygen binding affinity than HbA. Our group of medical scientists and clinicians conducted over 1260 cord blood transfusions with safe outcomes in all cases, as indicated in our published studies, from 1999 till date (follow-up) in children and adults for various indications. Not a single case of immediate or delayed immunological or non immunological reaction was reported.

    Keynote Speaker

    Time:
    10:10-10:50

    Title

    Title: Development of Epoxy-Tigliane Pharmaceuticals as Novel Therapeutics for Impaired Wound Re-Epithelialisation in Skin

    Ryan Moseley
    Cardiff University, UK
    Biography
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    Biography

    Ryan Moseley
    Cardiff University, UK

    Dr. Ryan Moseley is a Reader in Tissue Repair and Director of the MSc Programme in Tissue Engineering at Cardiff University, UK. Dr. Moseley’s research focusses on the mechanisms underlying dermal and oral wound healing responses during health and disease; and the development of stem cell-, biomaterial- and pharmaceutical-based strategies to address impaired healing in these tissues. Dr Moseley has been supported by funding bodies worldwide, including the MRC, NHMRC and Wellcome Trust, culminating in numerous published papers, filed patents with industrial partners in the dermal wound healing sector (Convatec, Systagenix Wound Management, Peplin/LEO Pharma, QBiotics); and many conference prizes.



    Abstract
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    Abstract

    Ryan Moseley
    Cardiff University, UK

    Dysfunctional woundrepair can cause significantly delayed re-epithelialization, leading to non-healing chronic wounds and burns. Management of chronic woundsand burnsposes significant challenges to Healthcare Services worldwide, confounded by acceptance that existing therapies are largely unsatisfactory. We are addressing such inadequacies, by evaluating the novel healing properties of epoxy-tigliane compounds, EBC-46 and EBC-211, isolated from seeds of the Fontain’sBlushwood Tree indigenous to Queensland’s tropical rainforest. Our industrial partner, QBiotics Ltd., is developing EBC-46 as an anti-cancer drug. In addition to its anti-cancer properties, EBC-46 stimulates exceptional healing following tumour destruction, manifested as enhanced wound re-epithelialisation, closure and minimal scarring. This work describes epoxy-tigliane effects on keratinocyte wound healing responses and their underlying mechanisms of action. Immortalized humanepidermal keratinocytes (HACATs) were treated with EBC-46 or EBC-211 (0-10µg/mL). Cell cycle progression/proliferation wereassessed by FACS analysis and MTT assay. HACAT migration was assessed usingin vitro scratch wounds/Time-Lapse Microscopy.Global gene expression changes induced by epoxy-tiglianes were quantified by Microarrays, with differentially expressed genes confirmed by protein level analysis. As epoxy-tiglianes mediate responses via classical protein kinase (PKC) activation, mechanistic studies were performed with BIM-1 (pan-PKC), Gö6976 (classical-PKC) and LY317615 (PKC-βI/PKC-βII) inhibitors. Western blotting confirmed phospho-PKC activation following epoxy-tigliane treatment. Both epoxy-tiglianesinduced significant HACAT cell cycle progression and proliferation at 0.001-10µg/mL.EBC-46 (0.001-0.1µg/mL) and EBC-211 (0.001-10µg/mL) also promoted significant HACAT scratch wound closure. Epoxy-tiglianessignificantly up-regulated genefor keratins, positive cell cycle/proliferation regulatory factors and matrix metalloproteinases; and down-regulated genes for other keratins and numerous cytokines, growth factors and chemokines. Enhanced proliferative and migratory responses were significantly abrogated by BIM-1 and Gö6976, although LY317615 exhibited minimal inhibitory effects.PKC activation increased following epoxy-tigliane treatment. Such findings explain the enhanced re-epithelialization responses in epoxy-tigliane-treated skin; and provide justification for their translational development as novel therapeutics for impaired wound re-epithelialisation.

    Keynote Speaker

    Time:
    11:05-11:45

    Title

    Title: Coding Potential of Physiological and Pathogenic Short Upstream Open Reading Frames

    Ioanna A Armata
    University of Moncton, Dr. Georges L-Dumont University Hospital Center, Canada
    Biography
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    Biography

    Ioanna A Armata
    University of Moncton, Dr. Georges L-Dumont University Hospital Center, Canada

    Dr. Armata is a molecular and cellular neuroscientist, who specializes in dystonia, a heterogenic group of debilitating neurological disorders, affecting both children and adults. Her training and expertise is in the fields of gene expression, transcription factors, functional non-coding mutations, assay development for drug high throughput screenings, and the CRISPR/Cas9 system. She obtained her Ph.D. in Neuroscience at Mount Sinai School of Medicine (2008), followed by a postdoctoral fellowship (2008-2012) at Massachusetts General Hospital and Harvard Medical School, and followed by a Research Faculty I appointment at Florida State University (2013-2016). She is currently a senior Research Fellow at the University of Moncton (Canada) studying translational therapeutics for dystonia syndromes and myotonic dystrophy 1. She has recently got an affiliation with the hospital Dr. Georges-L.-Dumont University Hospital Center, Canada.



    Abstract
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    Abstract

    Ioanna A Armata
    University of Moncton, Dr. Georges L-Dumont University Hospital Center, Canada

    Upstream translation initiation sites (uAUGs) and open reading frames (uORFs) are post transcriptional regulatory elements found in eukaryotic species, including fungi, plants and mammals. Functional uAUGs initiate translation within the 5 untranslated region (5’ UTR), and block a fraction of ribosomes to access the downstream cAUG of the coding region (CDS). Thus, they partially repress translation of the CDS to ensure CDS-encoded proteins do not exceed optimal levels. In addition to their role as translational repressors, some uAUGs initiate translation of short peptides (micropeptides).Innovations in computing, transcriptomics and proteomics have uncovered several uORF-encoded micropeptides. Many of these micropeptides exhibit significant selective constraint in their sequence, suggesting their functional relevance. Indeed, fora few uORF-micropeptides the cellular localization and specific cis- or trans -mediated roleshave been identified, that are different from the role of the downstream CDS-encoded protein. Upstream AUGs/uORFs can be either physiological orintroduced by single nucleotide polymorphisms (SNP) associated with human diseases. While translation of micropeptides from physiological uORFs has been well demonstrated, only three studies have examined translation of microproteins from SNP-introduced uORFs. Overall, the biological relevance of SNP introduced uORFs has been neglected. Lack of knowledge of the biological relevance of SNP introduced uATGs/uORFs-micropeptides prevents the development of related therapeutics.

    Sessions:
    Translational Medicine Approaches in Drug Discovery and Development & Cardio-Vascular Translational Medicine & Translational Therapeutics/Novel Therapeutic Technologies & Translational Neuroscience

    Time:
    11:45-12:10

    Title: Inhibition of Breast Cancer Bone Metastasis and Pancreatic and Colon Cancer by Synthetic Curcumin Analogs

    Mamoru Shoji
    Emory University School of Medicine, Winship Cancer Institute, Atlanta, USA

    Biography
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    Biography

    Mamoru Shoji
    Emory University School of Medicine, Winship Cancer Institute, Atlanta, USA

    Dr. Mamoru Shoji obtained his Medical Degree from the Hokkaido University, Japan, and completed internships at the US Naval Hospital, Yokosuka, Japan and the University of Pennsylvania in Philadelphia, residency in internal medicine at the Lahey Clinic, Boston, fellowship training in immunology at the Peter Bent Brigham and Robert Breck Brigham Hospitals (mentor, John R. David, MD), Harvard Medical School in Boston, in tumor immunology at the University of Minnesota (mentor, Charles F. Mckhann, MD from Massachusetts General Hospital) in Minneapolis, followed by fellowship in Hematology and Medical Oncology at Emory University (mentor, Charles M. Huguley, Jr, MD).



    Abstract
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    Abstract

    Mamoru Shoji
    Emory University School of Medicine, Winship Cancer Institute, Atlanta, USA

    Curcumin (diferuloylmethane) is a β-diketone constituent of the turmeric. It is used as a spice to give a specific flavor and yellow color to curry. However, its clinical efficacy is poor because of its low solubility. He worked with professors Liotta and Snyder at the Chemistry Department to synthesize a series of novel monocarbonyl analogs of curcumin (MACs) approximately 100 analogs including EF24, EF31 and UBS109. Dr. Shoji’s laboratory and the NCI tested the analogs for the anticancer activity. The NCI determined the mean growth inhibitory concentration (GI-50) of EF24, curcumin and cisplatin on the NCI-60 cancer cell panel, which are 0.7 μM, 7.3 μM and 9.5 μM, respectively. MACs do not kill normal breast cells MCF-10A but kill all cancer cells tested (KB-3-1, TU212, MiaPaCa, SE-Mel-28, RPMI-7951, and MDA-MB-231 cells) at concentrations (0-20 μM) [Zhu S, Current Cancer Drug Targets, 2014]. MACs inhibit NF-κB by inhibiting IKK-α and IKK-β. UBS109 inhibited breast cancer metastasis and osteolysis by inhibiting osteoclasts precursors and osteoclasts, but promotes new bone formation by stimulating osteoblast activation. UBS109 and EF24 inhibited four pancreatic cancer cell lines 100% at less than 1.25 μM, whereas gemcitabine did not up to 20 μM .UBS109 significantly inhibited MiaPaCa-2 pancreatic cancer xenografts and colon cancer (HT-29 and HCT-116) xenografts in mice at 25 mg/kg, iv once a week better than a combination of oxaliplatin (5 mg/kg) and 5FU (30 mg/kg) iv.

    Time:
    12:10-12:35

    Title: Immune Modulating Properties of the Anti-Cancer Preparation NSC631570

    Wassil Nowicky
    Nowicky Pharma and Ukrainian Anti-Cancer Institute, Austria

    Biography
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    Biography

    Wassil Nowicky
    Nowicky Pharma and Ukrainian Anti-Cancer Institute, Austria

    Dr. Wassil Nowicky Diplom-Ingenieur, Doctor scientiae technicorum, DDDr. h. c., Director of “Nowicky Pharma” and President of the Ukrainian Anti-Cancer Institute (Vienna, Austria). He has finished his study at the Radio technical Faculty of the Technical University of Lviv (Ukraine) with the end of 1955 with graduation to “Diplomingeniueur” in 1960 which title was nostrificated in Austria in 1975. Dr. Wassil became the very first scientist in the development of the anticancer protonic therapy and is the inventor of the preparation against cancer with a selective effect on basis of celandine alkaloids “NSC-631570”. He used the factor that cancer cells are more negative charged than normal cells and invented the Celandine alkaloid with a positive charge thanks to which it accumulates in cancer cells very fast. Thus, Dr. Nowicky is invited as an Honorable Speaker to take part in many scientific international congresses and conferences in USA, Australia, Japan, UAE, and Europe. Author of over 300 scientific articles dedicated to cancer research. Dr. Wassil Nowicky is a real member of the New York Academy of Sciences, member of the European Union for applied immunology and of the American Association for scientific progress, honorary doctor of the JankaKupala University in Hrodno, doctor “honoris causa” of the Open international university on complex medicine in Colombo, honorary member of the Austrian Society of a name od Albert Schweizer. He has received the award for merits of National guild of pharmasists of America and the award of Austrian Society of sanitary, hygiene and public health services and others.



    Abstract
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    Abstract

    Wassil Nowicky
    Nowicky Pharma and Ukrainian Anti-Cancer Institute, Austria

    Unusual for an anticancer agent NSC-631570 possesses some distinct immune properties [35, 49]. It was Prof. AndrejsLiepins of the St. John’s Memorial University, St. John’s, Canada who first pointed to this interesting fact. In the work with the C57BL/6 mice he revealed NSC-631570 to be an effective biological response modifier (BRM). After incubation with NSC-631570 the lytic activity of the splenic lymphocytes from the alloimmunised mice increased up to 48 fold (fig. 4). The immune modulating effect of NSC-631570 was studied in several studies in mice. Repeated subcutaneous injections of NSC-631570 to mice infected with the twofold LD50 of E. coli, S. aureus, or influenza virus increased the survival rate of the animals significantly. When human lymphocytes were incubated with phytohemagglutinin (PHA) and NSC-631570, increased absorption of 3H-thymidin in the cells was observed. The authors point out the strong synergetic effect of NSC-631570 and phytohemagglutinin. NCS-631570 induces immunogenic death of B16 melanoma cells and could restore antitumor activity of hypoxia-polarized macrophages. It suggests that NSC-631570 can be used for multimodal tumor therapy not only to kill the tumor cells, but also to stimulate a specific immune response to keep residual tumor (stem) cells and metastases under control. To investigate the adjuvant and immunomodulatory effects of the S.aureus cytoplasmic membrane extraction (CPM) in mono- and combined anticancer therapy outbred mice were transplanted with ascite and solid form of Ehrlich carcinoma followed by six day course of bacterial polymer used alone or in combination with cytotoxic anticancer drug NSC-631570. To estimate adjuvant effect tumor growth dynamics were evaluated, to characterize immunomodulating effect the number of circulating mononuclear phagocytes and their hagocytic activity were analyzed by flow cytometry. Our results suggest synergistic effect of PAMP and antineoplastic drug NSC-631570, that was accompanied by positive immunomodulation. The effects of cancer-selective drug NSC-631570 (Ukrain) used alone and in combination with pathogen-associated polymers of Gram-positive (peptidoglycan, lipoteichoic acid, and cytoplasmic membrane extraction of Staphylococcus aureus) and Gram-negative (Escherichia coli lipopolysaccharide) bacteria on mouse peritoneal macrophage metabolic activity in vitro are investigated. It is shown that NSC-631570, as used alone, causes a moderate enchancement of oxidative metabolism and arginase activity of intact peritoneal macrophages. The co-modulatory effect of the preparation depends on the initial functional state of phagocytes.

    Time:
    12:35-13:00

    Title: Synthetic Aromatse Inhibitors in the Treatment of Estrogen Dependent Breast Cancer

    Shagufta Waseem
    American University of Ras Al Khaimah, UAE

    Biography
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    Biography

    Shagufta Waseem
    American University of Ras Al Khaimah, UAE

    Dr. Shagufta joined the American University of Ras Al Khaimah as an Assistant Professor of Chemistry in the School of Arts and Sciences in August 2014. Before joining AURAK, she worked as an Adjunct Assistant Professor of Chemistry at the University of Modern Sciences, Dubai and American University of Ras Al Khaimah, UAE. She worked as a Postdoctoral Researcher Associate at the Department of Chemistry and Biochemistry, Oklahoma University, USA. She developed the noble drug delivery system for breast cancer drugs using carbon nanotubes and acquired the significant experience in nanotechnology and synthetic organic chemistry. She was appointed as a Postdoctoral Research Fellow and Visiting Scientist at Leiden/Amsterdam Centre for Drug Research (LACDR), Leiden, and the Netherlands. Her research interest was in silico prediction and clinical evaluation of the cardiotoxicity of drug candidates. She was focused to identify chemical substructures as ‘chemical alerts’ that interact with this hERG channel. She received a Ph.D. under the prestigious CSIR-JRF and SRF research fellowship in Chemistry from Central Drug Research Institute (CDRI)/Lucknow University, India in 2008, her PhD research work was in the field of estrogens and antiestrogens, design and synthesis of steroidal and non-steroidal tissue selective estrogen receptor modulators (SERMs) for breast cancer, 3D-QSAR CoMFA and CoMSIA studies and analysis of pharmaceutical important molecules. She has published 20 articles in peer-reviewed International journals of Royal Society of Chemistry, Elsevier, Wiley and Springer. And she teaches courses such as General chemistry, Organic Chemistry, Chemistry in Everyday Life, and Spectroscopy along with laboratory courses.



    Abstract
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    Abstract

    Shagufta Waseem
    American University of Ras Al Khaimah, UAE

    Breast cancer is the most common form of cancer present in women worldwide and is the second leading cause of death after lung cancer.1 In estrogen-dependent breast cancer, estrogen plays a significant role in the stimulation of breast cancer cell proliferation.2 Two main approaches have been developed to control or block the pathological activity of estrogens. The first approach involves the design and synthesis of estrogen receptor antagonist and inhibition of enzyme aromatase is the second approach for the development of new agents for the breast cancer treatment.3-5 Aromatase, an enzyme complex present in breast tissues, plays a substantial role in the biosynthesis of important endogenous estrogens from androgens. The source of oestrogen production in breast cancer tissues is intra-tumoral aromatase, and inhibition of aromatase may inhibit the growth stimulating effect of estrogens in breast cancer tissues. Consequently, aromatase is considered a useful therapeutic target in the treatment and prevention of estrogen-dependent breast cancer. Recently, different natural products and synthetic compounds have been rapidly developed, studied, and evaluated for aromatase inhibitory activity. Aromatase inhibitors are classified into two categories on the basis of their chemical structures, i.e., Steroidal and nonsteroidal aromatase inhibitors.6 This presentation will emphasize the potent role of synthetic steroidal and nonsteroidal aromatase inhibitors for the treatment of breast cancer.

    Time:
    14:00-14:25

    Title: Inhibition of NF-κB Pathway Attenuates the Multiple Organ Dysfunction Associated with Polymicrobial Sepsis in Mice with Pre-Existing Type 2 Diabetes Mellitus (T2DM)

    Sura Yahia Yosef Al Zoubi
    Queen Mary University of London, UK

    Biography
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    Biography

    Sura Yahia Yosef Al Zoubi
    Queen Mary University of London, UK

    Dr. Sura Al Zoubi is a clinical pharmacist who is doing a PhD in pharmacology at the department of the transnational medicine and therapeutics, the William Harvey Research Institute (WHRI), Queen Mary University of London, UK. Her main research interest is the cardiac dysfunction associated with sepsis and the effect of type 2 diabetes mellitus on the pathophysiology of cardiac dysfunction in sepsis. She has been working on the effect of NF-ĸB pathway inhibition on the multiple organ dysfunctions in sepsis. She has presented her work in many national and international conferences.



    Abstract
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    Abstract

    Sura Yahia Yosef Al Zoubi
    Queen Mary University of London, UK

    Introduction: Patients with diabetes are at higher risk of infections and sepsis. Activation of nuclear factor-κB (NF-κB) plays a substantial role in the pathophysiology of sepsis and diabetes. Here we investigate i) the effect of pre-existing type 2 diabetes mellitus on organ dysfunction (MOD) associated with sepsis and ii) whether inhibition of NF-κB using IKK-16 or linagliptin attenuates MOD in mice with sepsis and diabetes. Methods: Ten-week old male C57BL/6 mice received high fat (HFD) or chow diet for 12 weeks, and were subjected to caecal ligation and puncture (CLP) or sham surgery for 24 hours. At 1 hour after CLP, mice received IKK-16, linagliptin, or vehicle. Results: Administration of HFD resulted in a significant (i) impairment in glucose tolerance, (ii) (small) reduction in ejection fraction and, (iii) increase in alanine aminotransferase. HFD caused (Immunoplot analysis; heart) significant NF-κB pathway activation and expression of inducible nitric oxide synthase (iNOS). Mice on HFD subjected to CLP showed further (i) decline in EF, (ii) increase in serum ALT, and (iii) a significant renal dysfunction. Treatment of HFD-CLP mice withIKK-16 or linagliptin resulted in significant reduction of the CLP-induced i) MOD (cardiac/liver/renal), ii) NF-κB pathway activation, and iii) iNOS expression when compared to mice treated with vehicle. Conclusion: Our results show that HFD results in inflammation, cardiac dysfunction, and liver injury. Moreover, a pre-existing diabetic phenotype worsened the organ injury/dysfunction associated with CLP-sepsis. Most notably, inhibition of NF-κB reduced the organ injury/dysfunction caused by sepsis in animals with pre-existing T2DM.

    Time:
    14:25-14:50

    Title: Therapeutic Potential of Quinazoline Derivatives as Anticancer Agents

    Irshad Ahmad
    American University of Ras Al Khaimah, UAE

    Biography
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    Biography

    Irshad Ahmad
    American University of Ras Al Khaimah, UAE

    Dr. Irshad Ahmad joined the American University of Ras Al Khaimah in spring 2011 as an Assistant Professor of Chemistry. He received the master’s degree in chemistry from Jiwaji University in 1999. Subsequently acquired significant pharmaceutical industrial experience and developed cardio-selective beta-blocker drug molecule. He joined Central Salt and Marine Chemical Research Institute and Bhavnagar University under the sponsored project of DST and CSIR as a senior research fellow and received his PhD degree in chemistry in 2006. Subsequently, he accepted an invited scientist position in Korea Research Institute of Chemical Technology, South Korea and contributed his expertise in the field of Nanotechnology. And is a recipient of prestigious European fellowships (NWO-Rubicon & FCT) and he joined Van’t Hoff Institute for Molecular Sciences, University of Amsterdam, The Netherlands as a NWO Rubicon fellow (Netherlands Organization for Scientific Research, the Dutch Science Foundation), he acquired expertise in the field of supramolecular chemistry. Afterward, he moved to the Leibniz Institute for Surface Modification, Leipzig, Germany under the Deutsche Forschungsgemeinschaft Grant, he developed “Novel ultra-fast metathesis catalyst” for the production of high quality alternating copolymers. Subsequently he joined Department of Chemistry and Biochemistry, Stephenson Life Science Research Center, University of Oklahoma, USA as a postdoctoral research associate. He developed strategies for the novel environmentally friendly reactions for the production of value added chemicals from biomass. He is specialized in the area of chemistry, bridging the traditional disciplines of inorganic, organic and bio-organic chemistry. He contributed US and European patent for green and clean technology development. He has published peer-reviewed international research articles in the American Chemical Society (ACS), Royal Society of Chemistry (RSC) Cambridge, Elsevier Science, Wiley, and Springer journals. He has presented his research at several scientific conferences worldwide and received awards.



    Abstract
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    Abstract

    Irshad Ahmad
    American University of Ras Al Khaimah, UAE

    Cancer is one of the major causes of worldwide human mortality. It is estimated that about 1 688 780 new cancer cases will be diagnosed in 2017.1A wide range of cytotoxic drugs are available on the market, and several compounds are in different phases of clinical trials.2 Many studies suggest that these cytotoxic molecules are also associated with different types of adverse side effects; therefore researchers around the globe are involved in the development of more efficient and safer anticancer drugs. The heterocycles are widely investigated bioactive molecules and are considered important synthetic targets for the development of novel therapeutic agents.3 In recent years, quinazoline and its derivatives have been considered as a novel class of cancer chemotherapeutic agents that show promising activity against different tumors.4This presentation will comprehensively highlight the recent developments concerning the anticancer activity of quinazoline derivatives as well as offer perspectives on the development of novel quinazoline derivatives as anticancer agents in the near future.

    Time:
    14:50-15:15

    Title: Upstream Open Reading Frames in Rare Human Diseases and Related Therapeutics

    Ioanna A Armata
    University of Moncton, Dr. Georges L-Dumont University Hospital Center, Canada

    Biography
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    Biography

    Ioanna A Armata
    University of Moncton, Dr. Georges L-Dumont University Hospital Center, Canada

    Dr. Ioanna A Armata is a molecular and cellular neuroscientist, who specializes in dystonia, a heterogenic group of debilitating neurological disorders, affecting both children and adults. Her training and expertise is in the fields of gene expression, transcription factors, functional non-coding mutations, assay development for drug high throughput screenings, and the CRISPR/Cas9 system. She obtained her Ph.D. in Neuroscience at Mount Sinai School of Medicine (2008), followed by a postdoctoral fellowship (2008-2012) at Massachusetts General Hospital and Harvard Medical School, and followed by a Research Faculty I appointment at Florida State University (2013-2016). She is currently a senior Research Fellow at the University of Moncton (Canada) studying translational therapeutics for dystonia syndromes and myotonic dystrophy 1. She has recently got an affiliation with the hospital Dr. Georges-L.-Dumont University Hospital Center, Canada.



    Abstract
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    Abstract

    Ioanna A Armata
    University of Moncton, Dr. Georges L-Dumont University Hospital Center, Canada

    Translation generally initiates at the AUG codon (cAUG) marking the beginning of the coding region of a gene. Approximately 40% of human transcripts can also initiate translation within the 5’ untranslated region, at upstream AUG codons (uAUGs) which precede the cAUG. The presence of a uAUG within a transcript marks the beginning of an upstream open reading frame (uORF), which represents a potentially translatable nucleotide sequence. Single nucleotide polymorphisms that disrupt uAUG/uORF-mediated translation are associated with approximately 30 untreatable human diseases, such as melanoma, β-thalassemia, campomelic dysplasia and Dopa-Responsive Dystonia (DRD). Pathogenic uAUGs/uORF scan deregulate translation through two distinct molecular mechanisms: i) by reducing translation efficiency of normal protein products; and ii) by encoding mutant proteins that can trigger cellular death. Utilizing a uAUG/uORF associated with DRD, a high throughput screening assay was developed for identifying compounds that prompt the translational machinery to “bypass” pathogenic uAUGs. Screening of a small collection of bioactive compounds reveals that Salubrinal (SAL), - (a potent and selective inhibitor of eukaryotic initiation factor 2dephosphorylation)-, promotes overriding of pathogenic uAUGs associated with DRD, as well as with melanoma predisposition, and the Van der Woude syndrome. Evaluation of SAL against uAUGs associated with additional human diseases is required to determine if SAL is a promising therapeutic agent for the group of uAUG-associated diseases. Such therapeutic agents would satisfy an unmet medical need.

    Time:
    15:15-15:40

    Title: Microphysiological Systems: Organs on Chips for Drug Efficacy and Toxicity Studies

    Danilo A Tagle
    National Center for Advancing Translational Sciences, National Institutes of Health, USA

    Biography
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    Biography

    Danilo A Tagle
    National Center for Advancing Translational Sciences, National Institutes of Health, USA

    Dr. Dan Tagle is associate director for special initiatives at NCATS. He also recently served as acting director of the NCATS Office of Grants Management and Scientific Review and currently serves as executive secretary to the NCATS Advisory Council and Cures Acceleration Network Review Board. Prior to joining NCATS, Tagle was a program director for neurogenetics at the National Institute of Neurological Disorders and Stroke (NINDS), where he was involved in developing programs concerning genomics-based approaches for basic and translational research in inherited brain disorders. Prior to joining NINDS in 2001, Tagle was an investigator and section head of molecular neurogenetics at the National Human Genome Research Institute and has been involved in the highly collaborative effort toward the positional cloning of genes for Huntington’s disease, ataxia-telangiectasia and Niemann-Pick disease type C. He has served on numerous committees and advisory boards, including the editorial boards of the journals Gene and the International Journal of Biotechnology. Tagle obtained his Ph.D. in molecular biology and genetics from Wayne State University School of Medicine in 1990. He was an NIH National Research Service Award postdoctoral fellow in human genetics in the laboratory of Francis S. Collins, M.D., Ph.D., at the University of Michigan. Tagle has authored more than 150 scientific publications and has garnered numerous awards and patents.



    Abstract
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    Abstract

    Danilo A Tagle
    National Center for Advancing Translational Sciences, National Institutes of Health, USA

    The current drug development process is vulnerable to poor prediction of human physiological responses and failure to predict safety and efficacy of candidate drugs using current methods accounts for a much as 90% of the attrition rate. To address this challenge in drug development, the NCATS Tissue Chip for Drug Screening program https://ncats.nih.gov/tissuechip is developing alternative approaches for more reliable readouts of toxicity and efficacy. Tissue chips are bioengineered microphysiological systems utilizing chip technology and microfluidics that mimic tissue cytoarchitecture and functional units of human organs. These microfabricated devices are useful for modeling human diseases, and for studies in precision medicine and environment exposures. Tissue chips are poised to deliver a paradigm shift in drug discovery. By emulating human physiology, these chips have the potential to increase the predictive power of preclinical modeling, which in turn will move the pharmaceutical industry closer to its aspiration of clinically relevant and ultimately animal-free drug discovery.Near term uptake of these human-relevant platforms will fill gaps in current capabilities for assessing important properties of disposition, efficacy and safety liabilities. Tissue chips as novel preclinical modeling platforms offer a number of unique opportunities, with improved clinical predictions of human response being the most apparent and the greatest contribution. They may also provide a more efficient approach to mechanistic investigation, early safety liability screening and even more translationally relevant modeling of drug distribution and metabolism.

    Time:
    15:55-16:20

    Title: Meninges are a Reservoir for New Functional Neurons of the Cortex

    Francesco Bifari
    University of Milan, Italy

    Biography
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    Biography

    Francesco Bifari
    University of Milan, Italy

    Dr. Francesco Bifari, MD, PhD. is Principal Investigator and Assistant Professor at the Department of Medical Biotechnology and Translational Medicine, University of Milan, Italy. (Laboratory of Cell Metabolism and Regenerative Medicine.) In 2013 he was granted by FP7-PEOPLE-2013-IEF-No626829 grant and worked at the Laboratory of Angiogenesis and Neurovascular, VIB, Leuven, Belgium (Prof. Peter Carmeliet). He is the author of 33research papers (10 first, 3 last author) and 1 book chapter. Dr. Bifari have produced several top journal publications (Cell, Cell Stem Cell, Cell Metabolism, Cancer Cell, EMBO journal) He also has a score of 1350 citations; average citations per item=45, 3; mean Impact Factor=8, 6.



    Abstract
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    Abstract

    Francesco Bifari
    University of Milan, Italy

    Whether new neurons are added in the postnatal cerebral cortex is still debated. Here, we report that the meninges of perinatal mice contain a population of neurogenic progenitors that migrate to the caudal cortex and differentiate into Satb2+ neurons in cortical layers II-IV. These neurogenic meningeal cells are generated during embryonic development between E13.5 and E16.5. The embryonically derived meningeal progenitors remain largely quiescent, and in the first days after birth, they migrate to the cortex and differentiate to cortical neurons, without further proliferation. The resulting neurons are electrically functional and integrated into local microcircuits.Using multiple lineage tracing approaches, we found that most of the meninges-derived neurons belonged to the PDGFRß-lineage, while only a small fraction of cortical cells originating from meninges was derived from GLAST+ and Nestin+ lineages generated at E13.5.Since PDGFRß is expressed by both pericytes and a subset of radial glia (RG) cells, we hypothesized that the neurogenic meningeal cells belonged to one of these cell types. Single cell transcriptomic analysis identified a PDGFRß+meningeal cell population with a RG-like gene expression signature.We found meningeal cells with distinct transcriptome signatures characteristic of (i) neurogenic radial glia-like cells (resembling neural stem cells in the SVZ), (ii) neuronal cells, and (iii) a cell type with an intermediate phenotype, possibly representing radial glia-like meningeal cells differentiating to neuronal cells. Thus, we have identified a pool of embryonically derived radial glia-like cells present in the meninges that migrate and differentiate into functional neurons in the neonatal cerebral cortex. These findings broaden the concept of brain plasticity since they indicate that quiescent embryonically-born neural progenitors may contribute to add new functional neurons to the postnatal cortex

    Time:
    16:20-16:45

    Title: Isolated Mitochondrial-Transfer into Cells: Mechanism(s) and Therapeutic Potential

    Lorberboum-Galski Haya
    Institute for Medical Research Israel-Canada (IMRIC), Hebrew University of Jerusalem, Israel

    Biography
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    Biography

    Lorberboum-Galski Haya
    Institute for Medical Research Israel-Canada (IMRIC), Hebrew University of Jerusalem, Israel

    Dr. Haya Lorberboum-Galski is a Full Professor at the Department of Biochemistry and Molecular Biology, Faculty of Medicine, Hebrew University of Jerusalem. After receiving her Ph.D. in Biochemistry from the Hebrew University, she became a postdoctoral fellow at the Laboratory of Molecular Biology, NCI, and NIH, USA. Her main research area is Developing reagents for Targeted Human Therapy with the lately focus of mitochondrial genetic diseases. She published over 65 publications in peer-reviewed journals, review articles, edited a book on chimeric proteins and holds several patents. She served as the Head of the Department, Head of the Program for Biochemistry at the Faculty and many other committees. For the last five years she is the Chairman of the Institute for Medical Research (IMRIC) at the Faculty of Medicine, Hebrew University.



    Abstract
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    Abstract

    Lorberboum-Galski Haya
    Institute for Medical Research Israel-Canada (IMRIC), Hebrew University of Jerusalem, Israel

    Mitochondrial transfer of isolated mitochondria into host cells was reported over 30 years ago, and has been well established since then. However, while mitochondrial transfer’s beneficial effects are clear, the process itself is still vague. Our attempts to characterize mitochondrial transfer into cells showed that isolated human mitochondria can be transferred into many cell types and that mitochondrial transfer to mitochondria-defected cells results in beneficial outcomes for the cells. The exogenous transformed mitochondria co-localize with endogenous mitochondria. Heparan sulfated polysaccharide molecules are crucial for this process. In addition, the outer membrane and outer membrane proteins integrity are essential for the process. Pharmacological inhibition of macropinocytosis, but not of clathrin-mediated endocytosis, impeded the transfer. Transmission electron microscopy analysis of mitochondrial transfer revealed that the isolated mitochondria interact directly with cells, which engulf the mitochondria with cellular extensions. This suggests the involvement of macropinocytosis or macropinocytosis-like mechanisms in mitochondrial transfer, in line with our pharmacological inhibition tests. The simplicity by which mitochondria can enter cells in vitro, led us to evaluate mitochondrial transfer in vivo, in a mouse model of close head injury (CHI), a type of traumatic brain injury following both motoric and cognitive abilities, as well as in an Amyloid beta (Aβ) ICV injected mouse model for Alzheimer's disease. In both in vivo models, mitochondrial transfer was found to have a therapeutic effect.

    Time:
    16:45-17:10

    Title: Fingolimod (FTY720) as an Anti-Multiple Sclerosis Oral Ultimate Therapy

    Sara T Alrashood
    King Saud University, Saudi Arabia

    Biography
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    Biography

    Sara T Alrashood
    King Saud University, Saudi Arabia



    Abstract
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    Abstract

    Sara T Alrashood
    King Saud University, Saudi Arabia

    Multiple Sclerosis (MS) is a chronic progressive autoimmune disease. It has complex symptoms and challenges. Patients suffer the most from the inconvenience and intolerability till the old injectable disease modifying therapies. Therefore our research is highlighting the scoop on the newly available treatment using the oral therapies proceeding from their chemical nature and structure to prove their superiority to the traditional ones in controlling MS progression. This can lead to an improvement inlife quality for MS patients with the enhanced tolerability for oral drugs that is best achieved by using Fingolimod that is considered as the first approved oral drug for this disease.

  • Keynote Speaker

    Time:
    10:00-10:40

    Title

    Title: Protein Replacement Therapy for Mitochondrial Genetic Diseases

    Lorberboum-Galski Haya
    Institute for Medical Research Israel-Canada (IMRIC), Hebrew University of Jerusalem, Israel
    Biography
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    Biography

    Lorberboum-Galski Haya
    Institute for Medical Research Israel-Canada (IMRIC), Hebrew University of Jerusalem, Israel

    Lorberboum-Galski is a Full Professor at the Department of Biochemistry and Molecular Biology, Faculty of Medicine, Hebrew University of Jerusalem. After receiving her Ph.D. in Biochemistry from the Hebrew University, she became a postdoctoral fellow at the Laboratory of Molecular Biology, NCI, NIH, USA. Her main research area is Developing reagents for Targeted Human Therapy with the lately focus of mitochondrial genetic diseases. She published over 65 publications in peer-reviewed journals, review articles, edited a book on chimeric proteins and holds several patents. She served as the Head of the Department, Head of the Program for Biochemistry at the Faculty and many other committees. For the last five years she is the Chairman of the Institute for Medical Research (IMRIC) at the Faculty of Medicine, Hebrew University.



    Abstract
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    Abstract

    Lorberboum-Galski Haya
    Institute for Medical Research Israel-Canada (IMRIC), Hebrew University of Jerusalem, Israel

    Modern medicine offers no cure for genetic mitochondrial disorders and the usual treatment is mostly palliative. We developed a novel concept for the treatment of mitochondrial disorders using Cell/Organelle-Directed Protein Replacement Therapy; the delivery of a wild type mitochondrial protein/enzyme directly to its sub-cellular location and into its natural complexes, in the form of a fusion protein. Our approach is to fuse a wild type mitochondrial protein, including the Mitochondrial Targeting Sequence (MTS), with the delivery peptide TAT [HIV-transactivator of transcription (TAT) peptide], which will lead the protein/enzyme into the cells and their mitochondria, where it will substitute for the mutated endogenous protein. We tested this novel approach using a number of mitochondrial proteins, implicated in mitochondrial human diseases: Lipoamide Dehydrogenase (LAD), C6ORF66 (ORF), Frataxin (FXN) and methylmalonyl-CoA mutase (MCM), both in vitro, in patients’ cells and in vivo, in mouse models. TAT-MTS-Mitochondrial fusion proteins are rapidly and efficiently internalizing into cells and their mitochondria, both in patients’ cells and into mice tissues, including the brain. Treatment with the new TAT-MTS-Mitochondrial fusion proteins, improves mitochondrial functions and life span in animal models. One such fusion protein TAT-MTS-LAD is now being developed for human use. The novel approach may open new inroads in management of many incurable mitochondrial diseases.

    Keynote Speaker

    Time:
    10:55-11:35

    Title

    Title: Use of Freshly Collected Amniotic Membrane in Refractory Non-Healing Ulcers

    NiranjanBhattacharya
    Calcutta School of Tropical Medicine, India
    Biography
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    Biography

    NiranjanBhattacharya
    Calcutta School of Tropical Medicine, India

    Dr. Niranjan Bhattacharya holds a MD in Obstetrics and Gynaecology, MS in General Surgery and a DSC in Developmental Immunology. His principal specializations are cell and tissue therapy. Has presented Invited lectures in several international universities and institutions. Has published widely in international and national journals on cord blood and regenerative medicine; is the co-editor of five books on the subject published by Springer. Currently, Chair Professor and Head of the Department, Regenerative Medicine and Translational Science, and Director General, first Public Cord Blood Bank in India, Calcutta School of Tropical Medicine, Kolkata. Cited among top five global cord blood influencers by BioInformant.



    Abstract
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    Abstract

    NiranjanBhattacharya
    Calcutta School of Tropical Medicine, India

    A wound not showing any improvement or healing between 4 to 8 weeks can be classified as a chronic non-healing ulcer. Chronic non-healing ulcer is a major health problem globally. The etiology of non-healing ulcer includes venous, arterial, diabetic, atherosclerotic occlusion, traumatic and pressure ulcers etc. Diabetes is a major non-traumatic cause of chronic non-healing ulcers affecting mainly the lower limbs. Approximately 15-25% of diabetic patients develop diabetic foot ulcer (DFU) often resulting in amputation. Morbidity is high in many cases as healing is further complicated due to diabetic neuropathy and patients become susceptible to secondary infections due to altered immunity associated with diabetes. Application of dry, dehydrated or 1 percent glutaraldehide treated amniotic membrane for treating non-healing ulcers has been in practice for some time. The primary aim of the processed amniotic membrane is to act as a biological dressing model by preventing exudation and infection at the wound site and help in re-epithelialisation and suppression of fibrosis. However, most of these processed amniotic membranes might fail to directly participate in wound healing mechanism as they are devoid of cellular and growth factors, cytokine components which are predominantly lost during the time of chemical or physical processing of the amniotic membrane. Since 1999, Niranjan Bhattacharya and his associates, showed that application of freshly collected, unprocessed and serologically screened for infection, amniotic membrane, which is rich in inflammatory and non inflammatory cytokines, growth factors and progenitor cells, when applied within 4 hours of collection from lower uterine caesarean section, in patients suffering from traumatic and non-traumatic non-healing ulcers including refractory diabetic ulcers and arteritis induced ulcers, actively participates in wound healing process by formation of granulation tissues and complete re-epithelialisation, due to mesenchymal stem cells from the amniotic membrane.

    Sessions:
    Bio Molecular/Nuclear Imaging & Tissue Repair and Regeneration & Pharmacology (Cancer/Clinical) & Biomedical Sciences/Bioengineering

    Time:
    11:35-12:00

    Title: FasL Pleiotropic Role on Bone Marrow Stromal Cells and its Potential Regulation by Micro RNAs

    Maria Rita Rippo
    Marche Polytechnic University, Italy

    Biography
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    Biography

    Maria Rita Rippo
    Marche Polytechnic University, Italy

    Dr. Maria Rita Rippo was a student at the Department of Experimental Medicine, Policlinico Umberto I, of the University of Rome “La Sapienza 1993 –1994. She obtained her Degree in Biological Sciences from the University of Rome “La Sapienza”, in 1995. She has done her PhD from 1994-2001 Department of Experimental Medicine and Biochemical Sciences, Laboratory of Signal Transduction, including a 4 months collaboration and training period at the laboratory of “Apoptose, Cancer et Immunologie”, CNRS, Villejuif, Paris, France, directed by Guido Kroemer M.D. for Immunological Sciences & In 2000 she got the Fondazione Adriano BuzzatiTraverso post-doctoral fellowship, Department of Experimental Medicine and Biochemical Sciences, University of Rome “Tor Vergata” Laboratory of Signal Transduction. She was research fellow from 2001-2002 at Polytechnic University of Marche. Worked as a Researcher and consultant (2009- 2010) at the Center of Clinical Pathology and Innovative Therapies, Italian National Research Center on Aging (INRCA-IRCCS). Obtained her Specialization in Clinical Pathology (2015) University G.d’Annunzio, Chieti, 70/70 cum laude. Since 2002-2016 she is a Researcher in Experimental Medicine, Pathophysiology and Clinical Pathology Department of Molecular Pathology and Innovative Therapies, Polytechnic University of Marche. And is presently an Associate Professor in Applied Medical Technologies, Department of Molecular Pathology and Innovative Therapies, Polytechnic University of Marche.



    Abstract
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    Abstract

    Maria Rita Rippo
    Marche Polytechnic University, Italy

    Several lines of evidence suggest a pleiotropic role of FasL/CD95 on BM-MSC function. Although FasL was initially described as a T-cell-associated protein capable of inducing apoptosis by binding to its receptor Fas, a pleiotropic role in other cell populations has also been described. Fas engagement in resting T lymphocytes transduces inhibitory or costimulatory signals in a FasL dose-dependent manner, and in hematopoietic progenitors FasL receptor transduces dual apoptotic and trophic signals. Fas and FasL are expressed in freshly isolated BM–MSCs. However, cell death induction does not seem to be the Fas/FasL system’s main role in bone homeostasis. Fetal BM have functional extrinsic apoptotic pathways, whereas adult BM–MSCs are resistant to Fas-mediated apoptosis. FasL has a limited role in osteoblast and osteoclast apoptosis, but inhibits osteoblast differentiation in mice. We investigated the effect of FasL on BM–MSC apoptosis, proliferation, and differentiation into adipocytes to clarify the role of the Fas/FasL system in BM–MSC biology. FasL exerts a pleiotropic action on BM–MSCs depending on its concentration: low doses induce proliferation, whereas higher doses have a slight but significant apoptotic effect and, more importantly, inhibit adipogenesis; all such effects are exerted without affecting BM–MSC stemness, irrespective of dosage. Our findings show a FasL-dependent regulation of BM– MSC biology and adipogenesis, and suggest a role for FasL in conditions involving altered BM adipogenesis, such as osteoporosis in the elderly. Furthermore, our unpublished data show a modulation of several miRNAs during BM-MSC adipogenesis, Several of those regulating Fas/FasL expression, are cellular and circulating markers of aging and inflamm-aging (miR-21, miR-146a, miR-98 and miR-181a), Interestingly, plasma soluble Fas ligand concentration decrease whereas miR-21 miR-146a increase in elderly humans. Altogether these data suggest a functional axis involving miRNAs, Fas/Fasl system, bone marrow adipose tissue and aging.

    Time:
    12:00-12:25

    Title: Identification of T-Complex Protein 1 as a Novel Regulator of the Store-Operated Calcium Channel Orai1 Abundance at the Plasma Membrane

    Rawad Hodeify
    University of Ras Al Khaimah, UAE

    Biography
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    Biography

    Rawad Hodeify
    University of Ras Al Khaimah, UAE

    Dr. Rawad Hodeify earned his Ph.D. in Interdisciplinary Biomedical Sciences from the University of Arkansas for Medical Sciences, USA, in 2011, and M.S. in Biology from American University of Beirut, Lebanon. He received research training as postdoctoral fellow in Internal Medicine department at University of Arkansas for Medical Sciences and Weill Cornell Medicine before recently joining American University of Ras Al Khaimah as an Assistant Professor of Medical Biotechnology. His research work is focused on regulation of calcium signalling pathways during cellular development and differentiation and dissecting the crosstalk between cycle cell proteins and cell death pathways in kidney injury.



    Abstract
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    Abstract

    Rawad Hodeify
    University of Ras Al Khaimah, UAE

    Intracellular calcium (Ca2+) is a key signalling molecule. Store operated calcium entry (SOCE) is a fundamental Ca2+ influx pathway at cell membrane activated in response to intracellular Ca2+ store depletion. The SOCE machinery consists of ER-localized Ca2+ sensor, STIM1, and a Ca2+ selective channel at plasma membrane (PM), Orai1. At steady state, 40% of the total Orai1 protein pool localizes to PM while Orai1 cycles rapidly between PM and intracellular compartments. We discovered that a significant population of intracellular Orai1 pool localizes to a novel sub-PM vesicular compartment. Store depletion results in significant enrichment at PM. To identify Orai1-interacting proteins enriched in sub-PM vesicular compartment, we followed a quantitative proteomic analysis approach. TCP-1 (T -complex protein 1) was identified to be associated with Orai1 in sub-PM vesicular compartment. To functionally assess the role of TCP -1 in Orai1 sub-cellular localization, we knocked down TCP-1 in stable YFP-HA-tagged Orai1 CHO cells using RNA interference. Our data showed significant increase in surface Orai1 upon TCP-1 knockdown. Furthermore, we generated a mutant Orai1 in which the TCP-1-binding homologous region in the intracellular loop was scrambled. This mutant showed decrease binding to TCP-1, and 30% increase in surface Orai1. More importantly, the scrambled Orai1 mutant, when co-expressed with STIM1, showed faster TG-induced puncta formation, increased decay time after ATP-induced SOCE, and faster SOCE-dependent NFAT1 translocation. In summary, using an unbiased proteomics approach we successfully identified TCP-1 as a novel regulator of Orai1 abundance at PM. Disruption of TCP-1-Orai1 binding resulted in higher plasma membrane residence, faster puncta formation, and faster SOCE development. TCP-1, therefore, plays a key role in Orai1 residence at PM and controlling SOCE and intracellular Ca2+. These results demonstrate that TCP-1 is a novel regulator of Orai1 PM residence and activity, and introduce new directions for design of novel therapeutic strategies targeting SOCE.

    Time:
    12:25-12:50

    Title: Soluble Receptor for Advanced Glycation End Products (sRAGE) as Potential Biomarker for Diabetic Retinopathy and Chronic Kidney Disease

    Umah Rani Kuppusamy
    University of Malaya, Malaysia

    Biography
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    Biography

    Umah Rani Kuppusamy
    University of Malaya, Malaysia

    Dr. Umah Rani Kuppusamy is the Head of the Department of Biomedical Science, Faculty of Medicine, University of Malaya. She obtained her PhD in Biochemistry from the National University of Singapore in 1994. Her research interest revolves around free radicals, antioxidants and oxidative stress in diseases with predominant focus on the etiology and complications of diabetes, obesity and mechanism of action of micronutrients on oxidative stress. She has more than 80 publications in ISI-ranked journals, 130 conference papers, medals and awards and several patents to her credit.



    Abstract
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    Abstract

    Umah Rani Kuppusamy
    University of Malaya, Malaysia

    The global prevalence of Type 2 diabetes (T2D) which often leads to dire complications has increased significantly and 17.5% of adult population in Malaysia has T2D. Receptor for advanced glycation end-products (RAGE) is a multi-ligand, cell-surface receptor, which has been widely investigated for its role in the pathogenesis of complications with or without diabetic origin. RAGE also exists as other isoforms which include soluble RAGE (sRAGE) which acts as a decoy receptor that circumvents signal transduction originating from RAGE-ligand binding. Assessment of the levels of sRAGE and oxidative indices in diabetic patients with and/or without diabetic retinopathy (DR) or chronic kidney disease (CKD) and healthy control revealed mixed results. The soluble RAGE level of the patients with DR was significantly higher than healthy controls. Both sRAGE and pentosidine (an oxidative glycation marker) were significantly correlated with diabetes duration. The sRAGE/pentosidine was lower in patients with DR than the healthy controls. Logistic regression analysis revealed positive correlation between sRAGE/pentosidine ratio and the severity of DR and thus, it could serve as a biochemical tool for monitoring the progression of DR. Diabetic patients had significantly higher sRAGE levels in the presence of CKD or DR than in the absence of complications. However, the correlation between sRAGE and renal function in non-diabetic CKD was confounded by other factors but remained highly significant in diabetic CKD even after the adjustment of the potential confounding factors thus, serving as a more convincing indicator of the latter. These findings suggest that sRAGE can serve as a potential biomarker of DR and diabetic CKD. In view of the significant correlations between sRAGE and the severity of these complications, sRAGE could also serve as a tool for monitoring the progression of these complications.

    Time:
    14:00-14:25

    Title: Pharmacological Inhibition of LCK is Able to Revert Glucocorticoid Resistance in Pediatric T-ALL

    Valentina Serafin
    University of Padova, Italy

    Biography
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    Biography

    Valentina Serafin
    University of Padova, Italy

    Dr. Valentina Serafin graduated in 2008 in Medical Biology at the University of Padua, with a thesis performed in Germany on lung cancer progression and metastasis. Later on, in 2012, she achieved her PhD in Oncology and Surgical Oncology with a thesis regarding the role of Notch in Colorectal cancer process and metastasis diffusion. From June 2012 she is actively working at the Laboratory of Pediatric Oncohematology, University of Padua, where she is involved in the study of new biomarkers and or therapeutic targets by phosphoproteomic profiling of pediatric patients affected by acute lymphoblastic leukemia.



    Abstract
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    Abstract

    Valentina Serafin
    University of Padova, Italy

    Acute Lymphoblastic Leukemia (ALL) is the most common childhood malignancy. The probability of survival greatly improved during the last half century approaching 80%, but substantial numbers of patients still have poor outcomes. It is well established that initial unresponsiveness to the first week of glucocorticoids (GC) therapy predicts short-term disease-free survival, peripheral blood blast count after 7-day GC prephase is traditionally used to classify patients as Prednisone Good Responders (PGR, 5-years EFS 75%) or Prednisone Poor Responders (PPR, 5-y EFS 59%). The precise biologic factors leading to GC resistance have not yet been defined, thus in order to develop new patient-tailored approaches we performed a Reverse Phase Protein Analysis (RPPA) of 54 PGR and 33 PPR pediatric T-ALL patients and we studied the activation or expression of 87 proteins involved in key cellular signaling pathways. Interestingly, from the comparison between PGR and PPR patients, we found a higher expression of LCK Y505 (inhibited form) in PGR patients (p=0.001) together with a lower phosphorylation of SRC Y416 (active form). On the contrary, the phosphorylation in SRC Y416 resulted higher in PPR patients (p=0.01). Total LCK and Lck RNA expression were not differentially expressed in the two subgroups of patients, thus suggesting an increase activation of LCK in PPR patients. Indeed, in agreement with these results, also LCK downstream target PLCɣ, phosphorylated in Y783, resulted hyperactivated in PPR compared to PGR patients (p=0.05), confirmed also by a positive correlation between PLCɣ Y783 and SRC Y416 (r=0.51, p=0.01). Taken together, these results indicate an hyperactivation of the LCK pathway in PPR patients compared to PGR ones. LCK is part of the TCR multiprotein complex together with the GC receptor. After GC treatment the complex is disrupted, LCK activation is decreased and downstream prosurvival signaling inhibited, thus leading to cell death. In this light, an abnormally hyperactivated LCK could be able to sustain cell survival regardless GC activity. We thus tested if FDA-approved or recently developed LCK inhibitors would be able to revert GC resistance in T-ALL cells. We treated the GC resistant cell lines ALL-SIL, T-ALL1 and CEM with Dasatinib, Bosutinib, Nintedanib and WH-4-023 alone or in combination with Dexamethasone (Dex). All the four inhibitors alone are able to decrease cell survival, and very interestingly all of them strongly synergize with Dex, bringing to the sensitization of these cells to GC treatment. We also tested these compounds alone or in combination with Dex in primary PPR T-ALL cells derived from 5 different xenografts mice, and also in this case we observed a strong sensitization of these cells to GC treatment. Finally, as proof of LCK crucial role in GC resistance we observed a strong decrease in cell viability after Lck gene silencing and Dex treatment in ALL-SIL and CCRF-CEM cell line, and an increase GC resistance following LCK pathway hyperactivation in P12 ICHIKAWA GC sensitive cell and Dex treatment. Moreover, we observed that LCK hyperactivation in PPR patients upregulates the calcineurin/nuclear factor of activated T cells signaling triggering to interleukin-4 (IL-4) overexpression. GC-sensitive cells cultured with IL-4 display an increased resistance to dexamethasone, whereas the inhibition of IL-4 signaling could increase GC-induced apoptosis in resistant cells. Finally, treatment with Dex and Dasatinib also impaired engraftment of leukemia cells in vivo. Thus, our results strongly suggest that the inhibition of LCK using clinically approved drugs could represent a new additional therapeutic strategy to revert drug resistance in high-risk pediatric T-ALL patients, improving therapy response and patients quality life.

    Time:
    14:25-14:50

    Title: Proliferation of Porcine Adipose Derived Stem Cells in Herbal Scaffolds

    Franca Nneka Alaribe
    Tshwane University of Technology, South Africa

    Biography
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    Biography

    Franca Nneka Alaribe
    Tshwane University of Technology, South Africa

    Dr. Franca Nneka Alaribe, PhD Biomedical Sciences, University of Ferrara Italy, specializing in cellular/molecular pathology in cancer and degenerative diseases; MSc Molecular Biology/Biotechnology, Vrije University Brussels Belgium; BSc(Ed) Biology, University of Nigeria Nsukka. She is a researcher for over 10 years with high competence in biomedical research and has coordinated many research projects for NRF, THRIP, Bone South Africa and OSTA involving biomaterials. Presently she is working on stem cells and scaffold fabrication with South African medicinal plants. She has published more than 12 research works and academic papers in international peer reviewed journals, founder/editorial manager of Journal of Advances in Biomedical Studies. Editor of several peer reviewed journals and fellow of many scientific organisations.



    Abstract
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    Abstract

    Franca Nneka Alaribe
    Tshwane University of Technology, South Africa

    The significance and the potentials of in vitro cell culture studies are great considering the need for more cost efficient development of new drugs, time efficient treatment of cancer patients, and an understanding of developmental biology and mechanisms of stem cell differentiation. Cells, growth factors and scaffolds are the fundamental issues for tissue engineering. If porcine derived adipose stem cells (pADSCs) can effectively proliferate and differentiate when cultured on herbal scaffolds, this makes it a potential candidate for in vivo environment with possible profound impact on therapeutic application of herbal scaffolds. This study evaluated the in vitro differentiation capacity and anti-inflammatory effect of fabricated herbal scaffolds on pADSCs. To this effect, herbal scaffolds were developed by incorporating medicinal plant extracts (Eucomisautumnalis and Pterocarpusangolensis) and natural biopolymers (Alginate and chitosan) using lyophilisation technique. A standard sterility test on the scaffolds before in vitro use showed the ultraviolet radiation with 75% (v/v) ethanol to be suitable. pADSCs cultured on the herbal scaffolds were further monitored for in vitro proliferation and differentiation using different biological, immunological and genetic techniques. The identity of pADSCs were confirmed by positive FACs analysis of mesenchymal stem cell surface markers CD44, CD90 and CD105 (≥ 85%). Their multi potency was further evaluated by trilineage differentiation of pADSCs toward adipocyte, osteocyte and chondrocyte with histology staining. Scanning electron microscope (SEM) revealed that the herbal scaffolds possess an extremely porous structure than control (non-herbal scaffold). SEM and immunofluorescence results also revealed more attachment of ells at day 7, 14 and 21 on herbal scaffolds than non-herbal scaffolds. ELISA assay with IL-6 and gene expression of collagen type 11, alkaline phosphate, osteocalcin and osteopontin with RT-PCR confirmed the anti-inflammatory nature and mRNA expression/chondrogenic nature of the pADSCs cultured with the herbal Scaffolds media. This study indicates that pADSCs would have great therapeutic potential as seeding cells for in vivo transplantation to treat various inflammatory diseases and bone injuries when co-applied with medicinal plants and biopolymers.

    Time:
    14:50-15:15

    Title: Prognostic Value of the Expression of Endogenous Hypoxia Associated Proteins Hypoxia Inducible Factor-1 Alpha (HIF-1α) and Carbonic Anhydrase Isoform 9 (CAIX) Expressions in Breast Carcinoma

    Ola A Harb
    Zagazig University, Egypt

    Biography
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    Biography

    Ola A Harb
    Zagazig University, Egypt

    Dr. Ola A Harb, MD; completed her Pregraduate Medical Education (December 2005) in M.B.B.CH., with Total grade-Excellent from Zagazig University, Egypt. She obtained her Postgraduate/M.Sc (May, 2010) & M. D. (January 2015) in pathology from Zagazig University, Egypt. Dr. Ola is presently working as a Lecturer, at Department of pathology, Faculty of Medicine, Zagazig University, Egypt.



    Abstract
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    Abstract

    Ola A Harb
    Zagazig University, Egypt

    Background: Hypoxia has been found to be related to malignant initiation, progression, increasing the occurrence of metastasis and therapy resistance in many cancer types, which made a real need for discovering drugs that could antagonize the bad effect of hypoxia in cancer, decide which patients will have benefit from such anti-hypoxia therapy then to monitor response to therapy, especially in breast carcinoma. It is important to detect degree of hypoxia in each cancer that could be done by evaluation of the expression of hypoxia-associated protein in cancer biopsies e.g. hypoxia inducible factor-1 alpha (HIF-1α) and carbonic anhydrase IX (CAIX) and their detailed role in breast cancer is still uncertain and gives conflicting results. Aim of the Work: Was to evaluate HIF-1α and CAIX expressions in breast carcinoma, correlating their expressions with each other, with presence of lymph node & distant metastases, with recurrence free and overall survival rates of breast cancer patients. Methods: We evaluated HIF-1α & CAIX expressions in sections from 90 paraffin blocks of breast carcinoma using immunohistochemistry. We analyzed correlations between their levels of expressions, clinic-pathological and prognostic parameters of our patients. Results: HIF-1α and CAIX positive expression in breast carcinoma was related to advanced stage, presence of lymph node metastases, HER2 amplified and triple negative molecular subtypes (p<0.001), higher tumor grade (p= 0.001& 0.02 respectively) and negative ER (p= 0.005& 0.008 respectively) & PR (p= 0.009& 0.027 respectively) hormonal receptors, The expression of both markers was significantly positively correlated with each other (p<0.001). HIF-1α and CAIX positive expression in breast carcinoma was associated with shortened recurrence free and overall survival rates (p<0.001). Conclusion: HIF-1α and CAIX are markers of poor prognosis of breast carcinoma patients. Key words: Breast carcinoma, hypoxia; HIF-1α; CAIX; immunohistochemistry; prognosis

    Time:
    15:15-15:40

    Title: Papillary Thyroid Carcinoma

    Idania Teresa Mora López
    Enrique Cabrera General Teaching Hospital, Cuba

    Biography
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    Biography

    Idania Teresa Mora López
    Enrique Cabrera General Teaching Hospital, Cuba

    Dr. Idania Teresa Mora López Graduated in Medicine in 1990, Faculty of Medicine Julio Trigo Lopez, belonging to the Medical Sciences University of Havana. She obtained her First Degree Specialist in Comprehensive General Medicine and Specialist of First and Second Degrees in Endocrinology. And Diploma in Higher Medical Education, Master of Science Satisfactory Longevity & as a Aggregate Investigator. Presently she is Adjunct Assistant Professor of the Dr. Enrique Cabrera Medical Sciences University and the Latin American School of Medicine. She holds wide publications of 15 national / international.



    Abstract
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    Abstract

    Idania Teresa Mora López
    Enrique Cabrera General Teaching Hospital, Cuba

    The papillary thyroid carcinoma is the most frequent endocrine neoplasia and the one with the highest presentation in thyroid carcinomas, prevalence (5-6.5%), predilection for the female sex, second to third decades of life and increase in aging, influences predisposing factors such as head and neck radiation, thyroid nodule background, representing (5-15%), family history and the association with Multiple Endocrine Neoplasia type 2, Cowden syndromes, Gardner, Garney complex or unknown etiology. Diagnosis based on questioning, specifying exposed history, physical examination, determining consistency, location of the nodule with respect to the gland, size, regional lymph nodes, supraclavicular, growth pattern and complementary studies such as ultrasound that expresses whether it is solid, hypoechoic, irregular borders, microlobulated, microcalcifications, absence of safety halo, thick and incomplete halo, determination of thyroid function with Thyroid Stimulating Hormone (TSH), Thyroglulin and Fine Needle Aspiration Cytology, which according to the Bethesda System confirms carcinoma (97-99%) and diagnosis definitive with freezing biopsy and adenomegalies if they were removed. Treatment based on total thyroidectomy, later treatment with thyroid hormones (suppressive dose), follow-up with (TSH) per month, one year Gammagraphy and thyrogluline, according to the annual follow-up results in the first 5 years and every 2 years in the following 5 years, every 5 years the rest of the life, if it detects an area in the neck, perform treatment with 131IODO assess every 6 months and repeat at the same time until there is negativity and always doing thyroglycine. Treatments such as chemotherapy and tyrosine kinase inhibitors in non-operable and advanced cases.

    Time:
    15:55-16:20

    Title: Developing Patient-Specific Direct Neuronal Reprogramming for Modeling Neurodegenerative Disorders

    J Drouin-Ouellet
    Lund University, Sweden

    Biography
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    Biography

    J Drouin-Ouellet
    Lund University, Sweden

    Dr. Drouin-Ouellet has obtained her Ph.D. in Neurobiology at Laval University (Quebec City, Canada) in 2012. She is currently working at Lund University (Lund, Sweden) where she has developed a simple and efficient method for direct neuronal conversion of adult human dermal fibroblasts from patients with neurodegenerative diseases. She is now conducting research aiming at further advancing the direct neuronal reprogramming technology to provide patient specific based systems that faithfully recapitulate disease-associated phenotypes of neurodegenerative disorders in vitro.



    Abstract
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    Abstract

    J Drouin-Ouellet
    Lund University, Sweden

    Direct conversion of adult human fibroblasts into mature and functional neurons, termed induced neurons (iNs) was achieved for the first time five years ago. This technology offers a shortcut for obtaining patient and disease specific neurons for disease modeling, drug screening and other biomedical applications. Despite their great promise, reprogramming roadblocks have prevented the generation of iNs at a sufficiently high yield from adult dermal fibroblasts, which has significantly limited the adoption of this technology. To overcome this, we have developed a new highly efficient dual promoter-based vector system that results in efficient co-delivery of the two reprogramming factors Brn2a and Ascl1 in combination with either neuron specific microRNAs or the inhibition of the RE1-silencing transcription factor (REST). Global gene expression analysis showed that while both strategies resulted in induction of a neuronal program and similar level of neural conversion, the inhibition of REST induces the expression of additional genes that are related to neuronal identity and function. Based in this, we developed an optimized one-step method to efficiently reprogram dermal fibroblasts from elderly individuals using a single vector system and demonstrate that it is possible to obtain iNs of high yield and purity from aged individuals, including Parkinson’s disease patients. We are now evaluating the conversion capability of these skin fibroblasts and our preliminary results suggest that iN cells from sporadic PD patients reprogram in a similar fashion as that of healthy individuals and could thus serve as a tool to model intracellular pathological features associated with PD.

    Time:
    16:20-16:45

    Title: Treating Diet-Induced Obesity with Adipose-Derived Mesenchymal Stem Cells: Preclinical Evidence-Based Approach

    Fatima Saleh
    Beirut Arab University, Lebanon

    Biography
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    Biography

    Fatima Saleh
    Beirut Arab University, Lebanon

    Dr. Fatima Saleh is an Assistant Professor in the Faculty of Health Sciences at Beirut Arab University (BAU) since 2013. She obtained her BSc in Pharmacy in 2004 from BAU and MSc in Pharmacology and Biotechnology from UK. Dr. Saleh received her PhD degree in Biomedical Sciences from University of York, UK. Her current research interests focus on Mesenchymal stem cell research as well as identification of natural compounds with anti-diabetic, anti-oxidant or antimicrobial activity. She published in peer-reviewed journals and presented her work in many international conferences.



    Abstract
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    Abstract

    Fatima Saleh
    Beirut Arab University, Lebanon

    Introduction: Obesity has become a major healthcare issue over the past two decades, but its treatment is not yet optimal, especially in the long-term. The current status pressed the need for a novel treatment for obesity and its associated comorbidities. Stem cell-based therapy is emerging as a promising therapy for diet-induced obesity. The purpose of this study is to highlight the efficacy and safety of adipose derived stem cells (AD-MSCs) on obesity and related comorbidities in animal models, in order to establish the feasibility of translation into the clinical setting for a possible treatment in humans. Methodology: A Systematic review was conducted in adherence to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, and the protocol was registered in the PROSPERO registry (CRD42017077347). Findings: The initial search retrieved 578 papers, and seven articles met the inclusion criteria. Strong evidence reported the positive effect of AD-MSCs on obesity treatment in terms of body weight, glucose metabolism homeostasis, lipid profiles, non-alcoholic fatty liver disease and systemic inflammation. Conclusion: This study demonstrates the promising beneficial effects of AD-MSCs on obesity and obesity-related diseases such as type 2 Diabetes and dyslipidemia in animal models. However, more studies should be performed to understand their mechanism of action and to overcome some methodological limitations evidenced in our systematic review before moving forward to consider AD-MSCs transplantation into human.

  • Sessions:
    Stem Cells/Regenerative Medicine & Translational Stem Cell Research & Clinical and Translational Oncology & Scaffold in Regenerative Medicine & Nanofibers/Nanomedicine in Regenerative Medicine & Advances in Stem Cells and Regenerative Medicine

    Time:
    10:00-10:25

    Title: Stem Cells Improve Kidney Function and Remodelling In CRS Type II

    Chiara Castellani
    University of Padua, Italy

    Biography
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    Biography

    Chiara Castellani
    University of Padua, Italy

    Dr. Chiara Castellani, is the Assistant Professor in Technical Sciences of Laboratory Medicine. (University teaching of “Cyto and histopathological diagnosis” and part of courses of Pathological Anatomy.) Dr. Chiara got her Ph.D. in Cardiovascular Pathology (2007) & achieved thanks to a research on “Cardiac and non-cardiac stem cells in heart transplant and cardiac hypertrophy remodelling”. She completed her Specialty training in Clinical Biochemistry (March 2013). She has been a visiting research fellow at the Washington University in Seattle, WA (2006), where she worked under the supervisor ship of Prof. Charles Murry on the heart remodeling and stem cells. Research lines: i) Stem cells and cardiac remodelling; ii) stem cells and cardio renal syndrome; iii) cardiac amyloidosis; iv) Cardiac allograft vasculopathy; v) Exosomes and miRNA in heart and kidney transplantation. The outcome of her research was presented through oral presentations and posters during many national and international meetings. She had published papers in international ISI journals and one book chapter (HI=11 and citations)



    Abstract
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    Abstract

    Chiara Castellani
    University of Padua, Italy

    Background: We investigate the effects of human amniotic fluid stem cells (hAFS) and rat adipose tissue stromal vascular fraction GFP-positive cell (rSVC-GFP) therapy in a monocrotaliner at model of cardio-renal syndrome type II (CRSII). Methods: RHF was induced by monocrotaline (MCT) in Sprague-Dawley rats. Three weeks later, four million of hAFS or rSVC-GFP were injected via tail vein. BNP, sCreatinine, kidney and heart NGAL and MMP9, sCytokines, kidney and heart apoptosis (TUNEL technique) were studied. Stem Cells (SC) engraftment was detected with immunofluorescence. Results: SC treated rats showed a significant reduction of serum NGAL and Creatinine (NGAL 335.6±92.60 sCrea 0.36±0.05, p= 0.01) compared to CHF rats. In both hAFS and rSVC-GFP group, kidney protein expression of NGAL was significantly lower than in CHF group (SC 2.6*106±1.2*106 vs HF 5.1*106 ± 1.5*106 A.U., p=0.0008) and similar to that to controls. In both hAFS and rSVC-GFP treated rats, we observed a substantial number of SC engrafted in the medulla and differentiated in tubular cells. Apoptosis was significantly decreased (hAFS 10.29±10.81 and rSVC-GFP 24.82±25.19 cells/mm2, p=0.05 vs CHF) and similar to controls (9.85±7.2 cell/mm2). TUNEL-positive cells were mainly located in the kidney medulla. Pro-inflammatory cytokines were down regulated in SC-treated groups (p=0.05 vs CHF) and similar to controls. In SC treated rats, kidney and heart tissue NGAL was not complexed with MMP9 as showed in CHF groups, suggesting inhibition of MMPs activity. Conclusion: SC treatment produced improvement in kidney function in rats with CRSII. This may be the results of tubular regeneration due to SC engraftment, decrease tubular cells apoptosis and mitigation of pro-inflammatory milieu. Reduction of NGLA-MMP) complexion mainly to decrease MMPs activity with prevention of further negative heart remodeling

    Time:
    10:25-10:50

    Title: Primary Cancer Cell Cultures for Personalized Cancer Therapy

    Secil Yilmaz
    Genome Stem Cell Center at Erciyes University, Turkey

    Biography
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    Biography

    Secil Yilmaz
    Genome Stem Cell Center at Erciyes University, Turkey

    Dr. Yilmaz is Assistant Professor in Genome Stem Cell Center at Erciyes University. She worked with nobel laureate 2015, Aziz Sancar, at University of North Carolina during the PhD studies. Her current research involves cellular-based approaches to personalize the cancer theraphy.



    Abstract
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    Abstract

    Secil Yilmaz
    Genome Stem Cell Center at Erciyes University, Turkey

    Even though the last ten years have seen major discoveries in cancer research, cancer is still a global health issue. Most of cancer research are based on cancer cell lines and animal models. Immortal cancer cell lines are the most widely used models for investigating cancer biology but cell lines poorly represent the tumor heterogeneity of the cancer patients. The average rate of successful translation from animal models to clinical cancer trials are very low as a result of the traditional animal cancer models are limited in their ability to recapitulate the progression of cancer in human. Being able to transfer results from the lab to clinical studies and beyond is crucial. Primary cancer cells, by their very nature, are a useful tool in developing novel cellular therapies for personalized medicine and autologous treatments, by reason of the human primary cancer cells derived individual patients can closely mimic the origin of the disease. Each cancer patient needs to be considered as an independent individual with a unique disease since even in a same cancer disease, every single cancer patient has different genotypical/ phenotypical features. Therefore, the best personalized therapy should be the main subject of the cancer research. In addition, the application of primary cancer cell culture models has the potential to develop the three-dimensional (3D) tumor models for future cancer therapies and to determine biomarkers for diagnosis and treatments.

    Time:
    11:05-11:30

    Title: Development of a 3D Cell Culture Model Based on Biocompatible Polymeric Scaffolds Engineered with Human Mesenchymal Stromal Cells (MSCs) for Skin, Cartilage and Bone Regenerative Therapy

    Federica Re
    University of Brescia, Italy

    Biography
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    Biography

    Federica Re
    University of Brescia, Italy

    Dr.ssa Federica Re has obtained her Degree in Medical Biotechnology from 2010 to 2015 at the Department of Molecular and Translational Medicine of the University of Brescia, Italy. She is doing a PhD in Technology for Health at the department of Information Engineering at the University of Brescia, Italy. She spent several months at the Department of Biomedical Engineering at the University of Glasgow, Scotland during her PhD. Her main research interest is focused on the study of the human Mesenchymal Stem Cells applicationsin combination with biocompatible and bioresorbable scaffolds for a cost-effective regenerative therapy translatable into the clinical practice.



    Abstract
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    Abstract

    Federica Re
    University of Brescia, Italy

    Regenerative medicine aims to restore normal function by repairing or replacing damaged cells and tissues in patients. The efficacy and the success of regenerative medicine depends on many factors including the manner by which the cells are organized in the new tissue that must be able to mimic the structure and function of the original one. Current treatments for articular cartilage damage, bone defects and skin lesions are quite challenging and they show limited repair and regeneration following injury. This project aims at developing an innovative 3D cell culture model composed of Mesenchymal Stromal Cells (MSCs) and biocompatible, safe, resorbable, polymeric scaffolds for studying the mechanisms involved in tissue repair and treatment of chronic skin conditions, cartilage defects and bone lesions. For this purpose, hydrogel-forming polymers scaffolds of natural origin were firstly characterized for their mechanical and morphological properties, stability and degradability. Secondly, MSCs were seeded on these scaffolds and optimal culture conditions for MSCs expansion were defined. Preliminary results suggest that hydrogel scaffolds seem to be an optimal model to host MSCs. Currently, we are exploring the effects of scaffolds on modulating MSCs behaviour, in particular in the matter of how scaffolds can affect MSCs proliferation and differentiation. Moreover, efforts are being made to implement this 3D culture system with autonomous sensors in order to have an objective way to monitor tissue restoration. This project will provide new useful insights to define novel innovative therapeutic approaches, thus making this research translatable within the clinical scenario.

    Time:
    11:30-11:55

    Title: A New Polylipoic Acid-Based Nano-Platform for Heart Diseases Treatment

    Chiara Castellani
    University of Padua, Italy

    Biography
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    Biography

    Chiara Castellani
    University of Padua, Italy

    Dr. Chiara Castellani, is the Assistant Professor in Technical Sciences of Laboratory Medicine. (University teaching of “Cyto and histopathological diagnosis” and part of courses of Pathological Anatomy.) Dr. Chiara got her Ph.D. in Cardiovascular Pathology (2007) & achieved thanks to a research on “Cardiac and non-cardiac stem cells in heart transplant and cardiac hypertrophy remodelling”. She completed her Specialty training in Clinical Biochemistry (March 2013). She has been a visiting research fellow at the Washington University in Seattle, WA (2006), where she worked under the supervisor ship of Prof. Charles Murry on the heart remodeling and stem cells. Research lines: i) Stem cells and cardiac remodelling; ii) stem cells and cardio renal syndrome; iii) cardiac amyloidosis; iv) Cardiac allograft vasculopathy; v) Exosomes and miRNA in heart and kidney transplantation. The outcome of her research was presented through oral presentations and posters during many national and international meetings. She had published papers in international ISI journals and one book chapter (HI=11 and citations)



    Abstract
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    Abstract

    Chiara Castellani
    University of Padua, Italy

    Nanomedicine, that is the application of nanotechnologies to medicine, attracts an enormous interest. The aim of this study is to evaluate the safety, feasibility and biocompatibility of a new polylipoic acid-based nano-platform (NPs) for heart diseases treatment. Material and Methods: The lipoic acid polymerization reaction developed by Matile et al. has been used to create highly cross-linked polymeric nanoparticles. Dimeric and trimeric derivatives of lipoic acid with different spacers have been synthesized and used to produce surfactant stabilized nanoemulsions. Thiol-initiated polymerization of the microemulsions have been lead to the formation of a highly reticulated polymeric nanostructure. Loading of active molecules (such as rhodamine) has been obtained either by entrapment or by copolymerization of appropriate lipoic acid derivatives in the nanoparticle matrix. HeLa cells, Raw 264.7 cells, purified human leukocytes and human monocyte-derived. Macrophages were incubated with different concentrations of nanoparticles (up to 200 µg/ml) for 24h hours, the vitality was assessed by MTS assay and the association of NPs to the cells was assessed by cytofluorimetry. Red blood cells, purified by buffy coats of healthy donors, were incubated for 24h with different concentrations of nanoparticles (up to 200 µg/ml) and then the possible lysis of the red blood cells has been monitored by the release of hemoglobin measured at 540 nm. 18 male health Sprague-Dawley rats were injected with 10mg/Kg of NPs via vein tail. 7 male health rats were taken as controls. Rats were sacrificed 1hour, 3 hour, 24 hours 3 and 7 days after NPs injection and blood and organs were collected. Section of 2mm of lung, heart, liver, kidney and spleen were analyzed by Alliance 2.7 3D software to identify and quantify NPs-rhodamine conjugated. NPs localization in tissues was identify by confocal microscopy. Results: We found that in vitro this new polylipoic acid-based nano-platform didn’t exert any toxicity towards all the different cell types we used, even at high concentrations (200 µg/ml); NPs associate at low levels to all the tested cells, but they are captured by human macrophages at high levels. Moreover, NPs didn’t induce red blood cell lysis. In vivo, NPs fluorescence was identify immediately after injection in the heart. Moreover the heart was able to retain the NPs until 7 days after injection. The heart demonstrated to have a low clearance of NPs. Liver and kidney showed NPs fluorescence clearance at 3h after injection. Confocal microscopy showed that NPs are localize in the interstitium of organs and in the endothelial cells. NPs did not show any toxicity in the rats. Conclusion: Heart is able to retain NPs injected in blood flow for up to 7 days without evident negative side effects. These preliminary data suggest that this new nano-platform formulation could be used to target heart diseases and for therapeutic drug delivery.

    Time:
    11:55-12:20

    Title: Expression of Cox-2, Cyclin D1 and P21 in Colorectal Cancer Patients and Their Clinicopathological and Prognostic Significances

    Ola AHarb
    Zagazig University, Egypt

    Biography
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    Biography

    Ola AHarb
    Zagazig University, Egypt

    Dr. Ola A Harb, MD; completed her Pregraduate Medical Education (December 2005) in M.B.B.CH., with Total grade-Excellent from Zagazig University, Egypt. She obtained her Postgraduate/M.Sc (May, 2010) & M. D. (January 2015) in pathology from Zagazig University, Egypt. Dr. Ola is presently working as a Lecturer, at Department of pathology, Faculty of Medicine, Zagazig University, Egypt.



    Abstract
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    Abstract

    Ola AHarb
    Zagazig University, Egypt

    Background: Cyclooxygenase-2 (COX-2), play an important role in inflammation, carcinogenesis and cell cycle alterations. It is incriminated in cancer progression by causing dysregulation of normal cell cycle control. Cyclin D1 plays a vital role in cancer cell cycle progression. The activity of cyclin D1 can be blocked by CDK inhibitors, including p21 (cyclin-dependent kinase inhibitor-1A, CDKN1A, CIP1) that plays a role in regulating cell cycle. The purpose of this study: Was as to evaluate expression of COX-2, Cyclin D1 and P21 in colorectal cancer patients, analyze the relationship between their expression, clinicopathological criteria and the prognosis of patients. Methods: Expressions of Cox-2, Cyclin D1 and P21 were evaluated in 60 paraffin blocks colorectal cancer patients that were followed up for 3 years. The relationship between their level of expressions and prognosis of patients was analyzed. Results: Cox-2 & Cyclin D high expression was positively correlated with higher grade, advanced stage, presence of lymph node & distant metastasis and Duke stage (P=0.000). P21 high expression was negatively correlated with presence of lymph node metastases, higher grade (p=0.002), advanced stage, presence of distant metastasis and advanced Duke stage (P=0.001). We found a direct relationship between Cox-2 and Cyclin D 1, an inverse relationship between Cox-2 and P21, and an inverse relationship between Cyclin D 1 and P21 (P<0.001). Cox-2 & Cyclin D1 over expression and P21 low expression were positively associated with higher incidence of tumor recurrence (P=0.04, 0.000 respectively), higher incidence of cancer specific death (p=0.002, 0.004 & 0.000 respectively) but no significant correlation with response to therapy with all markers. Conclusion: High levels of expression of Cox-2 & Cyclin D1 are markers of poor prognosis, while high level of expression of P21 is a marker of good prognosis in colon cancer patients these results suggest that loss of control of cell cycle check points is a common occurrence in CC, and regulation in cell growth control and tumor suppression. Keywords: Cox-2, Cyclin D1, P21, colon cancer patients, immunohistochemistry, prognosis

    Time:
    12:20-12:45

    Title: Frontiers of Induced Pluripotent Stem Cells: From Bench to Bedside

    Rosy Joshi Mukherjee
    Center for Integrative Research on Cardiovascular Aging (CIRCA), Aurora Research Institute, USA

    Biography
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    Biography

    Rosy Joshi Mukherjee
    Center for Integrative Research on Cardiovascular Aging (CIRCA), Aurora Research Institute, USA

    Dr. Joshi-Mukherjee developed “Heart-on-µGMEA-Chip Model for cardiomyopathy” using cutting-edge technology namely, induced pluripotent stem cells and multielectrode array. The model reliably predicts cardiac cell death or altered electrophysiology phenotypes such as prolongation of action potential duration and early after depolarizations (EADs). She presented the research at Gordon Research Conference on Cardiac Arrhythmia and Mechanisms at Ventura, CA, United States, in 2017. During postdoctoral fellowship at Johns Hopkins University Dr. Joshi-Mukherjee received T32 fellowship for developing human induced pluripotent stem cell (hiPSC) lines from patient harboring sodium channel mutations associated with long QT 3 syndrome to investigate the mechanisms contributing to arrhythmia.



    Abstract
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    Abstract

    Rosy Joshi Mukherjee
    Center for Integrative Research on Cardiovascular Aging (CIRCA), Aurora Research Institute, USA

    Stem cell biology has gained tremendous interest in regenerative medicine, offering the hope of new therapies for otherwise intractable disease. Regenerative medicine involves the repair and regeneration of tissues for therapeutic purposes, such as replacing bone marrow in leukemia, cartilage in osteoarthritis or cells of the heart after a heart attack. Today advances in basic and clinical research make tissue regeneration feasible. This course is tailored for researchers with an interest in learning about current biological induced pluripotent stem research in a highly interactive setting. It aims to equip early researchers with the fundamental and cutting edge knowledge and critical understanding necessary for research in stems cells and the implications of induced pluripotent stem cell (iPSC) research for medicine and society. Participants will learn through multiple interfaces such as lectures, discussions, small group activities, and feedback from other participants. Explain the advantages and disadvantages of iPSCs as compared to embryonic stem cells. Describe various methods for creating iPSCs, including transfection methods using plasmids, retroviruses, small molecules, and adenoviruses. Discuss the advantages and disadvantages of each. We will explore basic mechanisms of how iPSC differentiate into specific tissues in response to a variety of biologic signaling molecules. We will discuss the use of such factors for in vitro tissue production. For example, bone morphogenetic proteins can be used in vitro to drive the differentiation of adult stem cells towards bone and heart. Discuss various in-vitro approaches for production of beating heart cells. We will also discuss how studies of the developmental, cellular and molecular biology of regeneration have led to the discovery of new drugswith examples from cutting-edge research. Discuss the clinical uses of iPS cells. Describe issues that must be resolved before iPS cells can safely be used in human cell-based therapy.

    Sessions:
    Poster Session

    Time:

    Title: Inhibition of Senescence and Promotion of the Proliferation of Chondrocytes from Articular Cartilage by CsA and FK506 Involves Inhibition of P38MAPK

    Deug Y Shin
    Dankook University College of Medicine, South Korea

    Biography
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    Biography

    Deug Y Shin
    Dankook University College of Medicine, South Korea

    Dr. Shin received his Phd in 1989 at the University of Tokyo, and worked as a Postdoc fellow and a research associate at NCI, USA. He was nominated as a chief of National Research Lab and a PM of National Cancer-Aging Research Program, and served as a Chair for Korean Assoaiciation of Genrontology and now serves as a professor and director of Aging-Cancer Center of Dankook Univ. He provided first evidence that p53 can induce senescence in human tumor and suggested a novel cancer therapy to induce senescence in human tumors.



    Abstract
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    Abstract

    Deug Y Shin
    Dankook University College of Medicine, South Korea

    CyclosporineA (CsA) and tacrolimus (FK506) are the most important immunosuppressive compounds that block the activation of helper T-cells. In this study, we investigated the effects of CsA and FK506 on growth and senescence of articular chondrocytes. Chondrocytesfrom young rabbit cartilage entered senescence after 8.6 ± 0.8 population doublings (PDs), while chondrocytestreated with CsA and FK506entered senescence after 12.3 ± 1.4 and 13.7 ±0.6 PDs, respectively. Furthermore, chondrocytes from the cartilage of old rabbits were senescent after 2.6 ± 0.9 PDs, whereas those treated with CsA and FK506were senescent after 8.2±1.8 and 6.9 ± 1.6 PDs, respectively. These compounds also inhibited senescence induction of chondrocytes in a high-cell density pellet culture system. We previously reported that p38MAPK plays a critical role in the onset of senescence in chondrocyte. This study revealed that the phosphorylation of p38MAPK was inhibited by either CsA or FK506. The early onset of senescence in chondrocyte harboring MKK6E, which is a constitutively-active form of MKK6 and increases p38MAPK phosphorylation, was blocked by CsA. These results suggest that CsA and FK506increase the proliferation and inhibit the senescence of articular chondrocytes through inactivation of p38MAPK. Key words: senescence, p38MAPK, CsA, FK506, chondrocyte.

    Time:

    Title: Decoding Ca2+ Signaling in Regulation of transcription Factor Activation and Cell Cycle Progression Using Optogenetics

    Wen-Tai Chiu
    National Cheng Kung University, Taiwan

    Biography
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    Biography

    Wen-Tai Chiu
    National Cheng Kung University, Taiwan

    Dr. Wen-TaiChiu received the Bachelor’s, Master’s and Ph.D. degrees from National Cheng Kung University, Taiwan in 1997, 1999 and 2007, respectively. He has been a postdoctoral fellow at the University of Texas MD Anderson Cancer Center from 2008 to 2010. Prof. Chiu is currently an associate professor in the Department of Biomedical Engineering at National Cheng Kung University. His research interests lie in the area of Ca2+ signaling and molecular imaging of cancers. Much of his work has been on improving the understanding, design, and performance of Ca2+ in focal adhesion dynamics, cell migration, metastasis and chemoresistance.



    Abstract
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    Abstract

    Wen-Tai Chiu
    National Cheng Kung University, Taiwan

    The ability of a simple ion such as Ca2+ to play an highly versatile intracellular signal results from the facility that cells have to shape Ca2+ signals in the dimensions of space, time and amplitude. Thus, spatial and temporal changes in intracellular Ca2+ concentration is important to determinate the cell fate. Optogenetics is the combination of genetics and optics tocontrol well-defined events within specific cells of living tissue in real time. Optogenetic stimulation approach that uses channelrhodopsin-2 (ChR2) related proteins has been developed for providing more precise and targeted stimulation effect on cellsin vivo and in vitro. We aimed to pose the formerly unaddressed fundamental question of how Ca2+ signals regulate transcription factor activationby manipulating intracellular Ca2+ through using optogenetic strategies. In this study, We found that (1) elevation of intracellular Ca2+ levels that correspond with the power, frequency and duty cycle of light illumination in a dose-dependent manner; (2) activation of Ca2+-dependent transcription factors is depends on Ca2+ oscillations with different frequency and amplitude; (3) cells in the various phases of the cell cycle showed different responses to Ca2+-mediated cell cycle progression. In summary, the delicate regulation and precise control of transcription factor activation and cell cycle progression can be achieved under the optogenetic platform. Parameters associated with light illumination will be optimized in the future. It will enable us to be confident in applying this advanced technique to (1) manipulate the expression patterns of genes by desire; and (2) control the growth and differentiation of cells.Such a process would be a potential platform in study ofcell development and cancer.

    Time:

    Title: Gene Discovery in a Neurogenetic Cohort

    Wilhemina K Koomson
    Yale University, USA

    Biography
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    Biography

    Wilhemina K Koomson
    Yale University, USA

    Wilhemina Koomson is a 3rd year PhD candidate in the Department of Genetics at Yale University. Her research incorporates bioinformatics in studying Neurological and Neurodevelopmental disorders. She completed her undergraduate work at Princeton University majoring in Molecular Biology.



    Abstract
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    Abstract

    Wilhemina K Koomson
    Yale University, USA

    We analyzed 1,505 patients with neurological/neurodevelopmental disorders of varying severity including brain structural malformations from a network of 28 clinical centers in Turkey, specifically ascertaining consanguineous cases. Next generation sequencing technologies, specifically whole-exome sequencing (WES), led to identification of disease causing variants in these cases. Our study considered various modes of inheritance, focusing on recessive forms of the disease as well as de novo variation, especially for non-consanguineous cases. We have identified several pathogenic mutations falling within a Homozygous by descent (HBD) segment in consanguineous families. With an improved filtering strategy we were able to identify multiple independent coding mutations or copy number variations (CNV), suggesting novel disease-causing genes have been identified. We prioritized these genes, as well as other strong candidate genes, based on known biological function, molecular interaction and Weighted Gene Co-expression Network Analysis (WGCNA). We identify gene co-expression module profiles of the new candidate genes, correlating them with the spatial and temporal expression patterns (during brain development) of known phenotype concordant disease genes.

    Time:

    Title: The Cytotoxic Effect of Pleurostylia Capensis Turcz (LOES)

    Nokukhanya Cebekhulu
    Mangosuthu University of Technology, South Africa

    Biography
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    Biography

    Nokukhanya Cebekhulu
    Mangosuthu University of Technology, South Africa

    Nokukhanya Cebekhulu is a board certified Medical Technologist specialised in Clinical Pathology with the Health Professions Council of South Africa. She is a Masters candidate at the Tshwane University of Technology in South Africa and is currently employed as a junior faculty in Biomedical Technology at the Mangosuthu University of Technology, Durban South Africa. Her research interests are in the indigenous knowledge systems of South Africa, specifically medicinal plants and their cytotoxic validation and potential translation and application in tissue engineering and bone fracture regeneration.



    Abstract
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    Abstract

    Nokukhanya Cebekhulu
    Mangosuthu University of Technology, South Africa

    Background: Bone fractures non-unions and delayed unions remain a persistent orthopaedic challenge. The current treatments have proven to have constraints due to numerous adverse side effects. Traditional medicinal plants have a reputable outcome in the treatment of many diseases. Pleurostylia capensis Turcz (Loes) is a rich source of bioactive metabolites known to be anti-viral, antibacterial, antiparasitic and antineoplastic. It is utilised to treat arthritis, fractures, epilepsy and other diseases for centuries. It is a rich source of bioactive metabolites. Objectives: To evaluate the cytotoxic activities of leaves and bark extracts Pleurostylia capensis against mouse skeletal (C2C12) cells invitro using the 3-(4,5-Dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Method: C2C12 cells were cultured as monolayers in medium supplemented with 10 % foetal bovine serum, and antibiotic cocktail. Subsequently, the cells were treated with the aqueous bark and root extracts of P. capensis at different concentrations.The MTT CellTiter 96® non-radioactive cell proliferation assay was conducted at day 2, 4, and 8 post- incubation. Results: The MTT assay results showed that P. capensis significantly increased the viability of the cells. The plant crude extracts enhanced cell proliferation and the percentage of viability with the highest peaks at Day 4, specifically on the positive control and concentrations 30µg/ml and 50 µg/ml. Conclusion: The results obtained revealed significant proliferation, overall metabolic activity, division, turnover and viability of cells. These findings warrant further studies to isolate novel compounds which will serve to inform future scientific research towards the development of safe drug formulations for bone fracture repair. Keywords: medicinal plants; bone fractures, cell culture, MTT assay.

    Time:

    Title: Prognostic and Predictive Values of Cell Cycle Proteins Centrosomal Protein 5 (CEPP 5) and Cyclin D1 Expression Inepithelial Ovarian Carcinoma (EOC)

    OlaAHarb
    Zagazig University, Egypt

    Biography
    χ

    Biography

    OlaAHarb
    Zagazig University, Egypt

    Dr. Ola A Harb, MD; completed her Pregraduate Medical Education (December 2005) in M.B.B.CH., with Total grade-Excellent from Zagazig University, Egypt. She obtained her Postgraduate/M.Sc (May, 2010) & M. D. (January 2015) in pathology from Zagazig University, Egypt. Dr. Ola is presently working as a Lecturer, at Department of pathology, Faculty of Medicine, Zagazig University, Egypt.



    Abstract
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    Abstract

    OlaAHarb
    Zagazig University, Egypt

    Background: Disturbances in the expressions of centrosomal proteins (CEPs) and regulatory proteins that control G1-Sphase transition, like cyclins could participate in dysregulation of cell cycle control that has been incriminated in the pathogenesis of several malignancies. Centrosomal protein 55 (CEP55) has an important role in participation in the final stage of cell division, and cell cycle progression. CEP55 and Cyclin D1 expressions were detected in several tumors but their prognostic and predictive roles in epithelial ovarian carcinoma (EOC) are still studied. Aim of the study was to explore tissue expressions of CEPP55 and Cyclin D 1 in EOC correlating their expression with pathological, clinical and prognostic parameters. Methods: CEP55 & Cyclin D1 expressions were evaluated in tissue biopsies that are retrieved from 60 cases of epithelial ovarian carcinoma using immunohistochemistry, patients that were followed up for 3 years. The relationship between their level of expressions and degree of differentiation, spread of the tumor, disease recurrence, response to therapy and survival were studied. Results: CEP55 expression in EOC was positively correlated with loss of differentiation of the tumor, presence of L.N (p<0.001), and distant metastases (p=0.012) & advanced stage of the tumor (p=0.007), cyclin D1 expression in EOC was positively correlated with loss of differentiation & advanced stage of the tumor, presence of L.N (p<0.001), and distant metastases (p=0.009). CEPP 55 & Cyclin D1 were positively correlated with each other. Low CEPP 55 & Cyclin D1 expressions were strongly correlated with optimal surgical eradication of the tumor, increased 3-year overall survival (OS) and low incidence of tumor recurrence after therapy (P <0.001). Conclusion: High levels of expression of CEPP 55 & Cyclin D1and are markers of poor prognosis in EOC patients. Keywords: CEP55, Cyclin D1 epithelial ovarian carcinoma, immunohistochemistry; prognosis

    Time:

    Title: L1CAM Up-Regulation in Association with p53 Over-Expression and E-Cadherin Down-Regulation can Help in Detection of Non-Endometrioid Foci, Risk Stratification, Relapse and Outcome of Endometrial Carcinoma Patients

    Ola AHarb
    Zagazig University, Egypt

    Biography
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    Biography

    Ola AHarb
    Zagazig University, Egypt

    Dr. Ola A Harb, MD; completed her Pregraduate Medical Education (December 2005) in M.B.B.CH., with Total grade-Excellent from Zagazig University, Egypt. She obtained her Postgraduate/M.Sc (May, 2010) & M. D. (January 2015) in pathology from Zagazig University, Egypt. Dr. Ola is presently working as a Lecturer, at Department of pathology, Faculty of Medicine, Zagazig University, Egypt.



    Abstract
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    Abstract

    Ola AHarb
    Zagazig University, Egypt

    Background: The recent guidelines for endometrial carcinoma (EC) management classify patients into; low-, intermediate-, high to intermediate and high-risk groups. Few numbers of patients in the category of low-risk disease were found to have relapse of the tumor that is not explained up till now. Moreover, it is essential to assess prognosis of other risk groups of EC. Also, the detection of patients that the adjuvant therapy will be more beneficial to them than other patients that will not require additional management after surgery is an essential aim of the recent researches about EC. So, recent studied has focused on detection of prognostic biomarkers that might improve risk stratification and detect which patients will need neoadjuvant chemotherapy after surgery. L1-cell adhesion molecule (L1CAM) is membrane glycoprotein member of immunoglobulin superfamily. P53 is a nuclear transcription factor and was found to be an established tumor suppressor. E-cadherin is an integral cell adhesion molecule and it is a component of adherens junction. The aim of our study to investigate the prognostic significance of L1CAM, P53 and E-cadherin expression in both early-stage, low-, intermediate-risk and high-risk EC, correlate their expression with clinicopathological criteria, tumor progression, recurrence, risk stratification of EC patients and with identification of patients that will need neoadjuvant chemotherapy after surgery. Methods: Expressions of L1CAM, P53 and E-cadherin were evaluated in 60 paraffin blocks EC patients that were followed up for 5 years. The relationship between their level of expressions, clinicopathological criteria and prognosis of patients was analyzed. Results: Positive expression of L1CAM was positively correlated with higher grade of the tumor (p = 0.043), presence of L.N metastases (p = 0.039), presence of, LVSI (p = 0.022), higher risk groups (p = 0.021), and presence of distant metastases (p=0.039). High expression of P53 was positively correlated with higher &advanced FIGO stage of the tumor, presence of L.N metastases, LVSI, higher risk groups and presence of distant metastases (p<0.001). Positive expression f E-cadherin was negatively correlated with higher grade of the tumor (p = 0.019), presence of L.N metastases (p = 0.010), presence of LVSI (p = 0.018) and presence of distant metastases (p=0.013). In multi variant analysis L1CAM expression is the most significant indicator of poor DFS & OS rates (p<0.001). We found a direct relationship between L1CAM, P53 an inverse relationship between L1CAM and E-cadherin, and an inverse relationship between P53 and E-cadherin (P<0.001). Conclusion: L1CAM & P53 over expression in addition to loss of E-cadherin expression in EC are associated with non-endometrioid subtype of EC, worse clinicopathological parameters, poor prognosis and could help in identification of patients in need for neoadjuvant chemotherapy after surgery Keywords: L1CAM, P53, E-cadherin, endometrial carcinoma, immunohistochemistry, risk stratification

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