Scientific Program

Day 1 :

Keynote Forum

Giulio Tarro

President of Foundation de Beaumont Bonelli for cancer research, Naples - Italy

Keynote: From sequence of tumor liberated protein (TLP) to potential targets for diagnosis and therapy

Time : 10:00-10:40AM

Biography:

Giulio Tarro graduated from Medicine School, Naples University (1962). Research Associate, Division of Virology and Cancer Research, Children’s Hospital (1965-1968), Assistant Professor of Research Pediatrics, College Medicine (1968-1969), Cincinnati University, Ohio. Oncological Virology Professor, Naples University (1972-1985). Chief Division Virology (1973-2003), Head Department Diagnostic Laboratories, (2003-2006). D. Cotugno Hospital for Infectious Diseases, Naples; Emeritus, 2006 -. Since 2007 Chairman Committee of Biotechnologies and VirusSphere, World Academy Biomedical Technologies, UNESCO, Adjunct Professor Department Biology, Temple University, College of Science and Technology, Philadelphia, recipient of the Sbarro Health Research Organization lifetime achievement award (2010). His researches have been concerned with the characterization of specific virus-induced tumour antigens, which were the "finger-prints" left behind in human cancer. Achievements include patents in field; discovery of Respiratory Syncytial Virus in infant deaths in Naples and of tumor liberated protein as a tumor associated antigen, 55 kilodalton protein overexpressed in lung tumors and other epithelial adenocarcinomas

Abstract:

A preliminary analysis of immunoprecipitation followed by Western Blotting (WB) shows corin and TLP precipitate at the same level (approximately 50 KDa) and are recognized by the same antibodies. In parallel the tests of immunoprecipitation were improved by the use of cell extracts derived from lung cancer cells A549 and NCI-H23 with the aim of obtaining a precipitate containing only the TLP. In fact the partial amino acid sequence of TLP shows a high homology with the sequence of human corin (only one amino acid is different) and is present in lung cancer under different isoforms. It is known that human corin is expressed mostly outside the cells and the protein extract derived from the extracellular medium and from the cells transfected with the plasmid, which overexpresses corin, shows several bands analysed on SDS-PAGE that are equivalent to the bands (about 50-100 KDa) observed in the WB analysed by anti-TLP. This protein band was identified as aldehyde dehydrogenase isoform 1A1 through mass spectrometry, revealing the molecular nature of at least one component of the previously described TLP complex. Next, we screened a cohort of 29 lung cancer patients (all histologies), 17 patients with non-neoplastic lung pathologies and 9 healthy donors for the presence of serum ALDH1A1 and global serum ALDH by enzyme-linked immunosorbent assay. This analysis indicated that the presence of ALDH was highly restricted to patients with lung cancer. Interestingly, the global ALDH test detected more lung cancer patients compared to the ALDH1A1-specific test, suggesting that other ALDH isoforms might add to the sensitivity of the assay. Our data suggest that ALDH levels may therefore be evaluated as part of a marker panel for lung cancer screening.Finally, the ability of the immune system to recognize a TAA, enables the development of a vaccine approach for preventive and therapeutic application and represents a main target of this field of research.

Keynote Forum

Sergey Suchkov

Chair, Dept for Personalized and Translational Medicine, Royal Society of Chemistry, UK

Keynote: Antibody-Proteases as a Novel Biomarker and a Unique Target to be applied for Biodesign and Bioengineering

Time : 10:40-11:30

Biography:

Sergey Suchkov graduated from Astrakhan State Medical University and awarded with MD, then in 1985 maintained his PhD at the I.M. Sechenov Moscow Medical Academy and in 2001, maintained his Doctorship Degree at the Nat Inst of Immunology, Russia. From 1987 through 1989, he was a senior Researcher, Koltzov Inst of Developmental Biology. From 1989 through 1995, he was a Head of the Lab of Clinical Immunology, Helmholtz Eye Research Institute in Moscow. From 1995 through 2004, a Chair of the Dept for Clinical Immunology, Moscow Clinical Research Institute (MONIKI. Dr Suchkov has been trained at: NIH; Wills Eye Hospital, PA, USA; Univ of Florida in Gainesville; UCSF, S-F, CA, USA; Johns Hopkins University, Baltimore, MD, USA. He was an Exe Secretary-in-Chief of the Editorial Board, Biomedical Science, an international journal published jointly by the USSR Academy of Sciences and the Royal Society of Chemistry, UK. At present, Dr Sergey Suchkov is a Chair, Dept for Personalized and Translational Medicine, I.M.Sechenov First Moscow State Medical University. He is a member of the: New York Academy of Sciences, USA; American Chemical Society (ACS), USA; American Heart Association (AHA), USA; EPMA (European Association for Predictive, Preventive and Personalized Medicine), Brussels, EU; ARVO (American Association for Research in Vision and Ophthalmology); ISER (International Society for Eye Research); PMC (Personalized Medicine Coalition), Washington, USA.

Abstract:

Catalytic Abs (catAbs) are multivalent immunoglobulins (Igs) with a capacity to hydrolyze the antigenic (Ag) substrate. In this sense, proteolytic Abs (Ab-proteases) represent Abs to provide proteolytic effects.Abs against myelin basic protein/MBP with proteolytic activity exhibiting sequence-specific cleavage of MBP are of great value to monitor demyelination whilst in MS. The activity of Ab-proteases was first registered at the subclinical stages 1-2 years prior to the clinical illness. And the activity of the Ab-proteases revealed significant correlation with scales of demyelination and the disability of the patients as well. So, the activity of Ab-proteases and its dynamics tested would confirm a high subclinical and predictive (translational) value of the tools as applicable for personalized monitoring protocols.Of tremendous value are Ab-proteases directly affecting remodeling of tissues with multilevel architectonics (for instance, myelin). By changing sequence specificity one may reach reduction of a density of the negative proteolytic effects within the myelin sheath and thus minimizing scales of demyelination. Ab-proteases can be programmed and re-programmed to suit the needs of the body metabolism or could be designed for the development of new catalysts with no natural counterparts. Further studies are needed to secure artificial or edited Ab-proteases as translational tools of the newest generation to diagnose, to monitor, to control and to treat and rehabilitate MS patients at clinical stages and to prevent the disorder at subclinical stages in persons-at-risks.

Keynote Forum

R Holland Cheng

Finland Distinguished Professor ,University of California, USA

Keynote: Discovery of Structural Modularity for Nanomedicine Design

Time : 11:30-12:15PM

Biography:

R Holland Cheng is Finland Distinguished Professor at University of California, USA
 

Abstract:

Structural proteins of viruses have the capacity to function both in assembly and in disassembly, which is made possible through a built-in flexibility triggered by cellular events.  Focusing on the highly selected viral capsid over their conformational domains between the metastable intermediates and the stable mature forms so far has provided us the essence of the needed stability, resisting extreme pH and digestive enzymes, to deliver medicals or agents to target tumors through both the circulation and the mucosal routes (1-3).  Aided by multimodal imaging integrated with the deep learning via convolutional neural network to guide the tracking and the targeting of the payloads, the design principles of inserting heterologous epitopes to target the mucosal surfaces will be exemplified regarding in this presentation. Deep learning has gained enormous attention by the success of its convolutional neural networks in demonstrated machine learning tasks including high-content image classification.  Crucial precision of cargo deliveries can be better realized through the AI deep-learning and the multiple modality of imaging domains to fully enable the targeting-engineered nanocapsids via various non-invasive mucosal routes. Further advancement of imaging technology like cryoEM and cellular tomography (see details in nobel.se; the Nobel Prize in Chemistry 2017) will be demonstrated in the unveiling of the associated molecular mechanisms essential to the platform vector design towards the success of constructing a non-invasive, mucosal targeting system (4-6).

Keynote Forum

Mark Feitelson

Professor

Keynote: Pharmacotherapy of chronic viral hepatitis and hepatocellular carcinoma

Time : 12:15-01:40PM

Biography:

Mark Feitelson is professor at Temple University, Philadelphia

Abstract:

Statement of the Problem:  Hepatocellular carcinoma (HCC) is the 5th most prevalent tumor type and second leading cause of cancer related deaths worldwide. The most common etiologies associated with HCC are chronic infections with hepatitis B and C viruses.  Although early HCC is curable by surgical resection, it is often asymptomatic and rarely diagnosed in time.  There are many treatment modalities used for patients with advanced HCC, but the efficacy of each approach is limited.  Sorafenib and other multi-kinase inhibitors have been approved for the treatment of advanced HCC, but these only extend life for up to a year.  Alterations in the composition of gut bacteria have been documented in HCC.  Since HCC arises on the background of chronic liver disease (CLD), experiments were carried out to test the hypothesis that the re-establishment of a normal gut microbiome would impact upon the pathogenesis of CLD and HCC.  Methodology: To test this hypothesis, a transgenic mouse model that expressed the hepatitis B oncoprotein, HBx, was used.  This model recapitulates most of the pathology and alterations in many molecular pathways that contribute to human HCC in 100% of the animals within 10-12 months.  Results: When these mice were fed with selected probiotics for several weeks prior to the appearance of dysplastic nodules, half the mice had no evidence of dysplasia, and the rest had smaller nodules and/or small regions of dysplastic cells.  Similar results were observed when mice were treated for several weeks before the appearance of HCC.  More than half the animals had no evidence of HCC, and those with tumors had fewer and smaller nodules.  Conclusions: These observations suggest that manipulation of the gut microbiome delay or block the pathogenesis of CLD and HCC.

  • Biochemistry

Session Introduction

A. B. Yazykova

Privolzhsky Research Medical University,Russia

Title: Hemoproteins and Elemental Homeostasis in Brain Tumors: Looking Inside the Pathways
Speaker
Biography:

A. B. Yazykova working at Federal State Budgetary Educational Institution of Higher Education “Privolzhsky Research Medical University” of the Ministry of Health of the Russian Federation, Nizhny Novgorod, Russia

Abstract:

The National Center for Biotechnological Information (NCBI) defines bioinformatics as a field of science in which biology, informatics and information technology merge into a single discipline. In bioinformatics there are three important sub-disciplines, such as the development of new algorithms and statistics, through which it is possible to evaluate the relationships between members of large data sets; analysis and interpretation of various types of data, including nucleotide and amino acid sequences, protein domains and protein structures; as well as the development and implementation of tools that provide effective access to and management of various types of information. An effective way to analyse metabolic changes is to build signal networks. The signal network is a probabilistic model of the transmission of a stream of biological information in a cell and between cells, tissues and organs through interactions of cellular agents of different origin. The structural element of the signal network is the binary interaction between two elementary objects. A higher-level component is a signal cascade or path represented by a set of consecutive interactions of partner molecules from the incoming signal to the final reaction associated with the initiation of a specific biological process: activation of gene group expression, opening of ion channels, assembly / disassembly and contraction of the cell cytoskeleton, division, apoptosis etc. The main elements of signalling pathways are proteins, since they are the main regulators of cell activity.

Primary tumors of central nervous system are a rare group of diverse tumors that account for less than 2% of all tumors, but are the fourth most common cause of cancer death. Despite of advances in neurosurgery, the development of intraoperative navigation, as well as chemo and radiation therapy, treatment of primary central nervous system tumors is still insufficiently effective.In the present study, the aim was to investigate blood and tissue macroelements, microelements and hemoproteins level in brain tumors, as well as their intermolecular interactions.

Results and discussion.

Modern databases of signaling pathways (KEGG) suggest that in normal cells the conditions of hypoxia can lead to HIF-1A protein synthesis. Besides, it is known, that chronic intermittent hypoxia (CIH) induces reactive oxygen species (ROS) generation, thereby increasing HIF-1 α expression. Detected reduced magnesium content in brain cancer cells can lead to decreasing of HIF-1 α activation, and probably, can serve as initiating agent for pathologic proliferation development. This factor, together with the protein p53 leads to synthesis and activation of proteins p21/27, which in turn inhibits CDK4/6 and leads to proliferation decrease. Intermittent hypoxia, leading to activation of the NOX enzyme, activates ROS synthesis, which inhibits the PHD enzyme and triggers the release of calcium ions. Calcium ions can be a triggering factor of two fundamental processes, apoptosis (often implemented under normal conditions) and cell proliferation via the Ras protein.  In glioma activation of protein synthesis of EGFR was shown, which, presumably, dramatically increases the release of calcium and thus activates the Ras protein, triggering uncontrolled proliferation. The effects of ROS on the release of calcium ions (Figure 1) may exacerbate this effect. There is evidence that under hypoxic conditions the cell produces myoglobin, which inactivates tumor growth and represents a factor of the cells adaptation to hypoxia. According to the literature a hypothetical relationship with MB is noted, as well as the expression of catalase, reduction of free radicals and oxidative stress

Conclusion.

This is one of the first studies to have examined intermolecular relationships between microelements, hemoproteins and antioxidant enzymes in gliomas. In hypomagnesemia, observed in cancer cells, HIF-1 α stabilization and activation by ROS is violated, and that leads to activation of cell pathological proliferation. Under the circumstances, increased Ca concentration via Ras-way activation leads to cell proliferation activation, more aggravating the situation. Combined disruption of mineral homeostasis and hypoxia, found in the present study, also can serve as factors, stimulating cell proliferation. Established increasing of hemoproteins activity, such as catalase and myoglobin, can possibly be considered as adaptation factor towards hypoxia, oxidative stress and element homeostasis violation.

Speaker
Biography:

Prakash Kinthada is a Professor in Chemistry at National institute Of Medical Sciences(NIMS) University, Jaipur, RAJASTHAN, INDIA.

Abstract:

Cancer is a dreadful disease and any practical solution in combating this disease is of paramount importance to public health. Cancer patients have burdened by drug induced toxic side effects, and no turned to seek help from the complementary and alternative medicine hoping for a better cure. Research on Platinum based drugs and Non Platinum based drugs is a Multi-Million Dollar Industry in USA and there is every need to produce safe drugs for the cure of this monstrous disease. Flavonoids have a long history of use in traditional medicines in many cultures. The phytochemical, curcumin is one of the major dietary flavonoid, belonging to a group of flavonol, Curcumin is a natural polyphenol. It is highly potential molecule capable of preventing and treating various cancers.  Various dietary chemo preventive agents, turmeric powder or its extract are broadly used as therapeutic preparations in Indian System of medicine. We provide a summarized synthesis and structural determination of Curcumin Oxime, Curcumin Thiosemicarbazone derivative of Gold (III) complex. The use of these analogs for prevention of cancer tumor progression and treatments of human malignancies. A pharmacologic agent for treating and/or preventing cancer, among other diseases and conditions, and particularly breast, prostate, and pancreatic cancer, in humans and animals. The novel pharmacologic agent is an isoflavonoid or isoflavonoid mimetic covalently attached to a cytotoxic pharmacophore that, preferably has the ability to conjugate with a metal salt to form a more potent metal complex, particularly a Au (III) complex and other complexes of Platinum, Palladium, Ruthenium, Copper etc.

  • MOLECULAR BIOLOGY
Speaker
Biography:

Lecturer-Bahri University – department of biochemistry and molecular biology

Abstract:

BACKGROUND: In this study we analyzed the effect of genetic mutations mainly Single nucleotide polymorphisms (SNPs) mutations that can alter the expression and functions of ATP1A2 gene as gene had been candidate to cause Migraine
METHODS: ATP1A2 gene was investigated in dbSNP/NCBI database in June 2016 and we used different computational analysis approach. Deleterious nsSNPs were predicted by SIFT and Polyphen-2 softwares. Then the damaging nsSNPs were submitted to I- mutant to Predict the change in stability due to mutation and PHD-SNP and SNPS&GO software used to demonstrate the relationship between SNP and related Migraine Protein structural analysis of amino acid variants was performed by Project Hope .To highlight genetic interactions of ATP1A2 we used Gene MANIA software.
 
RESULTS: Gena mania revealed that ATP1A2Gene encodes for the α2 subunit of ATPase Na+/ K. The SNPs sequence of ATP1A2 gene was collected from NCBI; 2576 of them [Homo sapiens] only From sift and polyphen-2 software the high score deleterious: SNPs were found as following: (rs28933401),) rs368405677), (rs121918612), (rs121918614), (rs121918615),( rs121918618), (rs121918619),( rs200425518), (rs181618883)and (rs149144720) Which analysis in Project HOPE software to analyzed the changing in amino acid properties and domains, , which found among these (rs). (rs28933401),) rs368405677), (rs121918612)have 100% mutation. Additionally, I-Mutant and PHD-SNPs and SNP&GO showed decrease instability for these nsSNP sup on mutation. Protein structural analysis with these amino acid variants was performed by using I-Mutant, Swiss PDB viewer, to check their molecular dynamics and energy minimization calculations.
 
CONCLUSION: in this study we found R689Q,T378N,G301R, D718N, P979L, T415M, R171W, A688P,A297T and G855E mutations in ATP1A2gene could directly or indirectly destabilize the amino acid interactions and hydrogen bonds networks thus explaining the functional deviations of protein To some extent mutations in ATP1A2 gene could directly or indirectly destabilize the amino acid interactions and hydrogen bonds networks thus explaining the functional deviations of protein to some extent.

Speaker
Biography:

Mr. Ghassan  has completed his Bachelor degree in Pharmacy  from University of Khartoum, then studied for a master degree in Genetics and Molecular biology at faculty of science University of Khartoum, he has been interested very much in CRISPR research applications since 2015 and has conducted an article review on CRISPR researches focused on molecular precision of CRISPR gene editing.

Abstract:

The explosion of genomic sequencing technologies combined with recent advances in genome-editing techniques has elevated the possibilities of genetic manipulations in numerous organisms in which these experiments were previously not readily accessible or possible. CRISPR/Cas9 is abbreviation of (Clustered Regularly Interspaced Short Palindromic Repeat)/ associated Caspase 9 (Cas9) protein (a nuclease enzyme) system, and it is derived from bacterial immune systems; it is emerging as a powerful tool for genome editing. Cas9 can be easily programmed to target new sites by altering its guide RNA sequence using computational methods; it can have many useful applications in biomedical human research and therapeutics.The goals of this review are to explain how CRISPR functions as a prokaryotic immune system, describe how researchers generate mutations with CRISPR/Cas9, highlight how Cas9 has been adapted for new functions, decrease the off-target effects for optimum therapeutic applications on humans and discuss ethical considerations of genome editing. Finally, the review also includes a case study and practical suggestions to incorporate CRISPR/Cas9 experiments into predicting the precision of gene editing of the Prostate Cancer fused genes (TMPRSS2:ERG).

Speaker
Biography:

Mahasen Ranatunga is a Principal Research Officer at the Plant Breeding division of Tea Research Institute of Sri Lanka, Talawakelle, Sri Lanka. He obtained his BSc (Agric.) Hons Degree from Faculty of Agriculture, University of Peradeniya. Later he earned a MSc in Biotechnology from Tamil Nadu Agricultural University, India and PhD (Plant Sciences) from the Post Graduate Institute of Science, University of Peradeniya. His expertise and current research interests are in tea breeding, molecular biology and biotechnology. He has authored 02 boook chapters, 20 research articles in peer reviewed journals and over 40 research communications and abstracts.  He is a recipient of Presidents awards for Scientific Publication in 2009.

Abstract:

The role of tea germplasm in crop improvement, though well recognized, yet lack sufficient information depriving its optimum use. About 600 accessions are conserved as tea germplasm and only 4% has been frequently utilized in breeding. The core collection captures the total genetic diversity of germplasm into a manageable size to enable utilization. The study was conducted to assemble a core collection of tea germplasm, using a holistic approach to facilitate management as a field genebank and to increase utilization in breeding.A representative sample of 93 accessions from the total collection was grouped based on the floral, biochemical and molecular diversity. The stepwise clustering in combination with random, preferred and deviation sampling strategies was employed in selection of entries to the core collection. The final core was selected based on the differences of traits between core collections and the germplasm evaluated using the coincidence rate (CR%) for range and the variable rate (VR%) for the coefficient of variation.Five major groups were identified based on floral traits and accessions were categorized into three major types China, Assam and Cambod  using pistil traits elucidating that the collection predominantly represented by Cambod followed by Assam types. Contents of proline, theanine and theobromine showed wide variations and dendrogram constructed using biochemical characters identified five major clusters. Six SSR primers generated 46 alleles with an average Polymorphism Information Content of 0.71. Fourteen - potential core collections were constructed and the collection developed using biochemical parameters and preferred sampling method was found to be the best with highest CR% of 102.25 and high VR% of 101.55.The study assembled the first core collection of tea germplam in Sri Lanka with 64 accessions to represent the total diversity which would facilitate the management with minimum cost, time and space.

Mehdi Ahmadifar

Royan Institute for Stem Cell Biology and Technology,Iran

Title: The Study of Effect of Amphetamine on Passive Avoidance Learning in Wistar Male Rats
Speaker
Biography:

Mehdi Ahmadifar is a research scholar at Royan Institute for Stem Cell Biology and Technology, Iran

Abstract:

Methamphetamine is sometimes prescribed by doctors for specific diseases that with the entering the central nervous system caused by a sudden release of categulamine and particularly dopamine in the brain. It stimulates brain cells, enhancing aggressive mood and increased body movement. The purpose of this study was to investigate, has been the effects of methamphetamine on passive avoidance learning and memory in adult male Wistar rats. Male Wistar rats of rats in the weight range (180-220gr) (N=6) was Divided into healthy group - control group (saline received) and dose received groups (1.5, 3, 5 mg/kg). Half an hour before the test, intraperitoneally injection was done and after the test, every day at specific times for long-term memory test for one week Injection was done. Results have shown that the incidence of passive avoidance between healthy and control groups there was no significant difference but there is a significantly decreased between the control group and the group receiving methamphetamine. Increase learning and short-term memory and reduced long term memory and passive avoidance learning mechanism is probably due to the involvement of the hippocampus in learning and memory consolidation and short term memory convert to long-term memory could potential mechanism of methamphetamineinduced damage to hippocampal neurons, particularly CA1 neurons. Meanwhile, short-term memory-enhancing effects of methamphetamine can result in Increase cortisol is also a short-term strengthens to the memory but in long term it will damage and weaken the memory.

Speaker
Biography:

Maryam Azimzadeh Irani has her expertise in understanding the structural roles of glycoconjugates at the atomic level. By working at the world-leading research groups in Singapore, Germany and Iran, she has gained a reliable background in the field of structural glycobiology. Her current research is mainly focused on the glycosylation of cancer mediated transmembrane receptors for developing anti-cancer therapeutics.

Abstract:

Epidermal Growth Factor Receptor (EGFR) is a glycosylated tyrosine kinase receptor associated with several cancers. EGFR plays an important role in cancer therapy and inspired several experimental and computational (molecular dynamics simulation) studies to investigate its function and dynamics. N-glycosylation is a critical aspect of EGFR functioning that was mainly unexplained until recently due to the challenges in obtaining and analysis of the structural data involving the glycan moieties. Latest simulations of glycosylated EGFR suggest atomistic mechanisms underlying the experimentally proposed functions of N-glycans in: EGFR increased ligand binding, reduced flexibility and arrangement within the cell membrane. It was shown that the increase in the ligand binding of glycosylated EGFR is mediated by the interaction between the two glycans attached to the growth factor binding subdomains resulting in stabilization of the growth factor binding site. Persistent hydrogen bonds’ formation between the glycans and EGFR contributes to proper folding and reduced flexibly of the glycosylated receptor. Assembly of the cell-integrated EGFR and its relative distance from the membrane are acquired by the lift-up action of the attached glycans. These findings can be used as a framework for implementation of computational techniques to obtain atomistic details of protein glycosylation as one of the most important areas of structural biology.

  • Drug Design and Biomakers

Session Introduction

Radim Nencka

Institute of Organic Chemistry and Biochemistry of the CAS,Czech Republic

Title: Structure-based approaches to novel antiviral compounds
Speaker
Biography:

Dr. Nencka is now group leader at the IOCB Prague. He is also a lecturer of Chemical Biology and Basic Principles of Drug Discovery at Palacký University, Olomouc. He got his Mgr. (equivalent of MSc.) in pharmacy from Faculty of Pharmacy in Hradec Králové, Charles University - his master thesis was done at University of Crete, Heraklion, Greece (Prof. Manolis Stratakis). He obtained Ph.D. in organic chemistry from Faculty of Science, Charles University, Prague (Dr. Hubert HÅ™ebabecký, Prof. Antonín Holý group at IOCB Prague) and spent his postdoctoral stay in Laboratory of Medicinal Chemistry, University of Ghent, Belgium (Prof. Serge Van Calenbergh). Among his main research interests are synthesis of novel compounds for treatment of viral diseases and rational design of inhibitors targeted on crucial enzymes.

Abstract:

Flaviviruses and picornaviruses are important groups of RNA viruses and both of them contain dangerous human pathogens, which threaten the lives of millions of people around the globe. Among others, Zika virus (ZIKV) has recently emerged as an important danger for human reproduction, causing significant malformations in newborns. Also, Dengue virus (DENV), another member of flaviviruses, causes around 96 millions symptomatic infections every year. On the other hand, human rhinoviruses (HRVs), members of picornaviruses, are probably the most common viruses causing infections in humans, since it is the major cause of common cold.Our research team is predominantly focused on the structure-based discovery of novel antiviral agents with special attention to these two groups of viruses. Recently, we have performed a study on novel potential antiviral compounds against ZIKV. We prepared a structural model of ZIKV RNA-dependent RNA polymerase in complex with the template and nascent RNAs, Mg2+ ions and accessing nucleoside triphosphate, which should serve as a functional tool for the design of novel nucleoside derivatives as a potential inhibitor of this central enzyme of viral replication. In addition, we have extensively studied potential novel antiviral agents against HRV based on inhibition of phosphatidylinositol 4-kinase IIIb (PI4KB), which is essential host factor required for assembly of replication organelles and the whole viral machinery inside human cells. The lecture will focus on utilization of structural information obtained by X-ray crystallography in the rational design of novel inhibitors of viral replication and try to explain potential strategies to effectively achieve this goal.

Day 2 :

  • Pathological Science

Session Introduction

Nouha Boubaker

Laboratory of proteins engineering and bioactive molecules (LIP-MB) , Tunisia

Title: Altered expression of miR-9, miR-143 and LMNA is related to clinicopathologic and epidemiologic features in bladder cancer in Tunisia
Speaker
Biography:

Nouha Boubaker working as a research scholar at Laboratory of proteins engineering and bioactive molecules , Tunisia

Abstract:

Urinary bladder cancer (BCa) is the second most common malignancy in Tunisian male patients. Hsa-miR-9 and hsa-miR-143 have been reported to be deregulated in many types of tumors.Recent evidences indicate a regulatory role of these miRNA’s in BCa genesis and progression.They interact with many targets such as LMNA or K-RAS that are implicated in intracellular signaling pathways known to be deregulated in BCa like PI3K,mTOR or MAPK.The aim of the present study was to investigate the prognosis and the biological impact of miR-9,miR-143 and LMNA deregulation in Tunisian BCa patients. 90 cases were included and were divided in low and high grade non muscle‑invasive BCa (LG/HG NMIBC) and muscle‑invasive BCa (MIBC).Risk groups of recurrence and progression were established using the EORTC scoring. The expression patterns of miR-9, miR-143 and LMNA were defined using RT- QPCR and the2-deltadeltaCTmethod.Association to clinicopathological factors was analyzed using the student test and Pearson correlation.Our data indicated a high expression of miR-9 and LMNA and a low expression of miR-143 in tumors compared to non-tumoral controls (p<0.05). miR-9 and miR-143 expression showed different profiles between NMIBC and MIBC (p=0,002, p=0,001 respectively) but only miR-9 shown a discriminating patterns between (LG NMIBC) vs (HG NMIBC) (p value =0,008).Then,the up-regulation of miR-9 was associated to progression (p=0,037) and exposure to occupational carcinogens (p=0,02) and the down-regulation of miR-143 was associated to the intensity of tobacco use (p=0,04), alcohol consumption (p=0,04) and multifocality (p=0,04).Finally,a significant correlation was revealed between miR-9 and LMNAmRNA expression levels (p=0.0001; r=0.913) and miR-143 and LMNAmRNA (p= 0,001).These positive associations were only found in the LG NMIBC group. We concluded that these associations could be considered as “driver events” of BCa tumorigenesis and that miR-9 indirectly influence LMNA expression through the interaction with other targets mRNAs.These hypotheses should be confirmed by further functional studies.

  • Molecular Biology Methods & Techniques
Speaker
Biography:

Mousa O. Germoush working as a Faculty of Science at Aljouf University, Saudi Arabia

Abstract:

The present study aimed to investigate the possible protective mechanisms of diosmin against cyclophosphamide (CP)-induced liver injury in rats, focusing on oxidative stress, inflammation and apoptosis. Materials and Methods: Rats were administered diosmin at doses 50 and 100 mg kg–1 weeks prior to CP injection. Two days after CP administration, rats were sacrificed and samples were collected. Results: The CP administration induced liver injury evidenced by the histopathological changes and significant increase in liver marker enzymes, lipid peroxidation and nitric oxide levels. Liver reduced glutathione (GSH) and antioxidant enzymes were significantly declined. Gene expression and protein levels of the pro-inflammatory cytokines, tumor necrosis factor alpha and interleukin 1 beta were significantly increased in liver of CP-administered rats. Pre-treatment with diosmin counteracted CP-induced oxidative stress and inflammation. In addition, diosmin protected against CP-induced apoptosis as assessed by down-regulation of BAX and up-regulation of Bcl2 at both gene and protein levels. Conclusion: The present study provides evidence that diosmin exerts protective effect against CP through induction of antioxidant defenses and suppression of inflammation and apoptosis. These findings represent a novel protective mechanism of diosmin against CP-induced hepatotoxicity.

  • Molecular Biology
Speaker
Biography:

Asmaa Ibrahim is Chemist at Diagnostic and research unit of parasitic diseases (DRUP), Kasr Al-Ainy Faculty of Medicine, Cairo University, Cairo, Egypt

Abstract:

Background and Objectives: The pathogenic bacterium Helicobacter pylori (H.Pylori) and intestinal parasites (IPs) especially Cryptosporidium are well-known for their high prevalence in pediatric patients worldwide especially in developing countries like Egypt. Identifying associations between both infectious agents due to sharing the same mode of infection estimated risks and predictive factors for susceptibility to co-infection.This study conducted to determine the prevalence of H.pylori and Cryptosporidium co-infection in diarrheic Egyptian children by copro PCR restriction fragment length polymorphism (PCR-RFLP), studying their estimated risk and prospective factors.Methodology: Fecal samples were collected from 226 pediatric patients, 125 diarrheic which include both (immunocompetent and immunocompromised) and 101 non diarrheic as a control group. All samples were submitted to coproscopic examination for detection of intestinal parasites before and after concentration, acid-fast stain for coccidian parasites detection such as Cryptosporidium and copro PCR restriction fragment length polymorphism (PCR-RFLP) targeting Cryptosporidium oocyst wall protein (COWP) gene for Cryptosporidium and urease subunit alpha (UreA) gene targeted for H.pylori. Further coproimmunoassay tests were performed only for immunocompromised cases to detect Cryptosporidium and H. pylori coproantigen as a rapid test.Result: Among the studied    population positive for giardiasis by microscopy (58%) were co-infected with H. pylori and positive cases for cryptosporidiosis by PCR (70%) also were co-infected with H. pylori. Additionally among the studied    variables only immune status (immunocompetent/immunocompromised), diarrhea, vomiting, fever, feeding milk and associated parasites (G. intestinalis and Cryptosporidium) were significantly associated (PË‚0.05) with detection of H.pylori by using multivariate analysis using logistic regression. To our knowledge .No studies demonstrated the co infection between H.pylori and cryptosporidium. Among studied variables immunity status, diarrhea, weight loss, gender and polyparasitism were significantly associated (p<0.01) with Cryptosporidium and H.pylori co- infection.Conclusion: Our results shed light on fundamental role of   Intestinal parasites such as CryptosporidiumGiardia co-infection with H.pylori. Whether H.pylori provides a favorable condition for intestinal parasitosis or vice versa still needs further investigation, emphasis upon determining correlation with gut micro biomes.

  • Biochemistry

Session Introduction

Dina Hajjar

University of Jeddah,Saudi Arabia

Title: Bio-prospecting of natural resources in Saudi Arabia for new potential bioactivity
Speaker
Biography:

Dina Hajjar working as faculty of Science at University of Jeddah,Saudi Arabia

Abstract:

Natural products offer a unique opportunity to discover new active compounds due to their chemical structure and their biodiversity.  From ancient years natural products are in several medical applications. New approaches to advance the drug discovery path are required to innovate the invention of new leads compounds. Saudi Arabia natural resources have not been widely inspected with regard to their biological activities. Here, we discuss the hidden potential of Saudi Arabia’s natural resources namely terrestrial medicinal plants. Saudi Arabian traditional plants were chemically extracted and fractionated using Solid Phase Extraction method (SPE). Ziziphus mucronata, one of the tested plants from the Jeddah region, showed Ziziphus mucronata has inhibitory effects on cell proliferation and causes cell cycle disruption activity. Moreover, using histone H2AX phosphorylation as a marker for DNA damages revealed that the tested compounds possibly induced DNA double stranded breaks. Further experimental evidence suggests an inhibitory effect on Topoisomerase II making it a suitable candidate for further evaluation as a potential lead for the treatment of cancer.

Speaker
Biography:

Rahma Said working as a research scholar at National Institute of Applied Science and Technology - University of Carthage, Tunisia

Abstract:

Currently, microRNAs (miRs) represent great biomarkers in cancer due to their stability and their potential role in diagnosis, prognosis and therapy. This study aims to evaluate the expression levels of miRs-1260 and -1274a in prostate cancer (PC) samples and to identify their eventual targets by using bioinformatic analysis. In this project, we evaluated the expression status of miRs-1260 and -1274a in 86 PC patients and 19 controls by using real-time quantitative PCR and 2-ΔΔCt method. Moreover, we retrieved validated and predicted targets of miRs from several datasets by using the “multiMir” R/Bioconductor package. We have found that miRs-1260 and 1274a were over-expressed in PC patients compared to controls (p<0.0001). Moreover ROC curve for miRs-1260 and 1274a showed a good performance to distinguish between controls group and PC samples with an area under the ROC curve (AUC) of 0.897 and 0.784 respectively. However no significant association could be shown between these two miRs and clinical parameters. Finally, a bioinformatic analysis revealed the association between these two miRs and several targets implicated in prostate cancer initiation pathways. In conclusion our data suggest that miRs-1260 and -1274a might be eventual diagnostic biomarkers for PC.

  • Structural & Molecular Biology

Session Introduction

Muhammad Zafar Iqbal

Sichuan Agricultural University Sichuan, China

Title: Mysterious meiotic behavior of autopolyploid and allopolyploid maize
Speaker
Biography:

Muhammad Zafar Iqbal has expertise in maize cytogenetic and allopolyploid’s evolution. His research contribution shed the light on evolution and relationship of subgenomes in genus Zea. He offered a new mechanism for origin and evolution of the genus Zea species on basis of his research findings. His laboratory is famous in China for classical cytogenetic techniques; Genomic in Situ Hybridization (GISH) and Fluorescent in Situ Hybridization (FISH). These techniques have been well utilized to understand the genomic relationships and evolutionary consequences of species.

Abstract:

This study was aimed to investigate the stability of chromosomes during meiosis in autopolyploid and allopolyploid maize, as well as to determine an association of chromosomes between maize (Zea mays ssp. mays Linnaeus, 1753) and Z. perennis (Hitchcock, 1922) Reeves & Mangelsdor, 1942, by producing a series of autopolyploid and allopolyploid maize hybrids. The intra-genomic and inter-genomic meiotic pairings in these polyploids were quantified and compared using dual-color genomic in-situ hybridization. The results demonstrated higher level of chromosome stability in allopolyploid maize during meiosis as compared to autopolyploid maize. In addition, the meiotic behavior of Z. perennis was relatively more stable as compared to the allopolyploid maize. Moreover, ten chromosomes of “A” subgenome in maize were homologous to twenty chromosomes of Z. perennis genome with a higher pairing frequency and little evolutionary differentiation. At the same time, little evolutionary differentiation has been shown by chromosomes of “A” subgenome in maize, while chromosomes of “B” subgenome, had a lower pairing frequency and higher evolutionary differentiation. Furthermore, 5IM + 5IIPP + 5IIIMPP and 5IIMM + 5IIPP + 5IVMMPP were observed in allotriploids and allotetraploids respectively, whereas homoeologous chromosomes were found between the “A” and “B” genome of maize and Z. perennis.

Speaker
Biography:

Kurganov Sardarkhodja working as research scholar at Republican Centre of Forensic Expertise,Uzbekistan

Abstract:

When determining the degree of solution on the paternal line, if discrepancies between the child's father and other paternal relatives are not taken into account, population-specific mutation rates should be used to determine if this is a mutation or a true exception. Therefore in this study, we aim to determine the mutation rates of 17 Y-STR(Y-filer PCR Amplification Kit) loci in Uzbekistan.Within the framework of the research, the speed of mutations in 300 pairs of fathers and sons throughout Uzbekistan was studied. Among 5100 translations of alleles, mutations were detected in seven cases, giving an average mutation rate of 7/5100 = 1.373 * 10-3 at all loci by generation.Also, the rate of mutations in two large related families from districts Zangiotа and Kibray was studied. According to the data obtained the first family consisted of 15 generations, and the second family consisted of 14 generations. As a result of our analysis, one mutation was detected in each family of the locus DYS385a.As a result of our study of 150 people living in the city of Angren, it was revealed that they had a genetic similarity of the Y chromosome. Among this random sample, 80 people who had close haplotypes, turned out to be relatives. Among them, in the study of loci with a high mutation frequency, 19 individual mutations were found.The total number of mutations per sample (19 mutations) is divided by the number of haplotypes (11 haplotypes) and the number of markers in the haplotype (17 markers)  (Mutations per haplotype)In this sample study, the average observed number of mutations per marker is 0.101604.Now we can approximately estimate the age of the common ancestor. The rate of mutations for our 17-marker haplotype: 0.031 mutations per haplotype, or 0.0018 mutations per marker. The duration of one generation is assumed to be 25 years.The age of a common ancestor is obtained by dividing the average observed number of mutations per marker by the rate of mutations (also on the haplotype): generations.Multiplying 55.71 generations of 25 years, we obtain 1392 years. 1390 years is an approximate, rough estimate of the age of a common ancestor.