Biography:

Gantois’ career started at the University of Antwerp, where she received her PhD in the laboratory of Dr. Frank Kooy at the Center of Medical Genetics, studying gene expression changes in the brain of Fragile X KO mice. They were the first ones to show downregulation of the  GABA_A receptor in Fragile X syndrome. Afterwards, she joined the group of Dr. John Drago at the Howard Florey Institute in Melbourne, Australia, where she studied Parkinson’s and Huntington’s disease using conditional KO mouse models. Following, she returned to Belgium and joined the Laboratory of Biological Psychology at Leuven University, studying the importance of dopaminergic pathways in spatial and non-spatial learning. At present, Dr. Gantois is in the Sonenberg laboratory at McGill University in Montreal, and is studying the importance of translational control in diseases such as autism. They showed that metformin, an anti-diabetic drug and translational inhibitor, can rescue autistiform features in a mouse model of Fragile X syndrome.

Abstract:

Fragile X syndrome (FXS), the leading single gene cause of autism and the most common form of hereditary intellectual disability, is caused by the silencing of the FMR1 gene and subsequent loss of FMRP. Loss of FMRP expression leads to enhanced activation of the mTORC1 and ERK signaling pathways in the brain of FXS patients and Fmr1 knockout mice. Consistent with increased ERK activity, eIF4E phosphorylation is elevated in the brain of FXS patients and Fmr1 knockout mice. Metformin, the most widely used anti-type 2 diabetic drug, represses the ERK and mTOR pathways. In this study, we treated Fmr1 knockout mice over 10 days with metformin. Fmr1 knockout mice show impaired social interaction and increased grooming, which was corrected after metformin treatment. Also, metformin treatment reduced the incidence of audiogenic seizures in the Fmr1 knockout mouse. Hyperactivity was not rescued after metformin treatment. Furthermore, metformin treatment rescued the excessive LTD and dendritic spine abnormalities observed in Fmr1 knockout mice, and also reduced the testicular weight. Using western blot, we showed selective normalization of MEK/ERK signaling pathway and consequently reduction of phospho-eIF4E and MMP-9 after metformin treatment, while levels of phospho-S6 remained elevated. The changes in ERK signaling, and not mTOR signaling, after chronic metformin treatment are possibly due to the rescue of elevated expression of B-Raf and c-Raf in the Fmr1 knockout mouse. Together, metformin might be a novel therapeutic approach to restore specific behavioral and morphological aspects of FXS and ASD. 

Keywords: Fragile X Syndrome, Autism, Metformin, Mouse

Biography:

Alain Chapel is scientific investigator at IRSN. He has been developing cell therapy to protect against the effects of radiation. He collaborates with clinicians to strategies for treatment of patients after radiation. He has participated in the establishment of proof of concept of the therapeutic efficacy of MSCs. He is a member of national and international societies. He is associate editor of World Journal of Stem Cells, World Journal of Gastrointestinal Surgery, World Journal of Radiology, The Open Gene Therapy Journal and Journal of Clinical Rehabilitative Tissue Engineering Research. He has participated in the scientific organization of international conferences.

Abstract:

Cell therapy was demonstrated of main importance in the management of normal tissue radiation damage. Preclinical and clinical trial data suggest that mesenchymal stem cells (MSCs) are a practical and safe source of cells for stem cell-based therapies of severe tissue damage consecutive to radiation overexposure. MSCs were shown to migrate to damaged tissues supporting wound healing through a “cell drug” mode of action restoring skin and gut functions after irradiation. However, technical limits associated with large-scale ex vivo expansion indicate that alternative source is required to obtain sufficient cell numbers of the appropriate lineage to treat patients with severe disease.

Based on this pluripotency and unlimited expansion potential, induced pluripotent stem cells (iPSCs) are considered a promising resource for regenerative medicine. Like naturally occurring stem cells, these artificially induced cells can self-renew and develop into almost any cell in the body (pluripotency). Clinical iPSC banks of selected universal donors should allow their use for large scale allogeneic grafts.

Our consortium describes a GMP-grade system to produce hiPSCs, a cell population capable of reconstituting human hematopoiesis. We demonstrate that i) hiPSC-derived hematopoietic stem cells (HSCs) from healthy donor are capable of reconstituting a functional human hematopoiesis in a radio-induced aplasia preclinical model, ii) hiPSC-derived HSCs from aplastic anemia patients or acute leukemia affected patients retain this ability.

Our study prepares a new approach of autologous graft (from the cells of the patient) of cells for healthy tissue damage after radiation exposure.  It could potentially pave the way to the constitution of universal banks of stem cells, which would radically increase the capacity of support and treatment of tissue exposed to high doses of ionizing radiation and in the management of chronic late radiotherapy side effects.

Biography:

Anna Landsman is a lecturer and researcher in the Lev Academic Center of Jerusalem. She He received a bachelor’s degree in  Dnipropetrovsk State Medical Academy (Ukraine), a master’s degree in and PhD degree in Human Physiology from Hebrew University in Jerusalem, Israel. She complited a postdoctoral fellowship in Hadassah Medical Center, Jerusalem. Her research interests include human physiology, molecular mechanism underlines psychiatric disorders, gene therapy approach for cancer treatment

Abstract:

Postpartum depression (PPD) is a disease which incorporates a variety of depressive states differing in nature and severity. To assist in the understanding of the pathogenesis of the disease, we aimed to ascertain a molecular mechanism underlying PPD development. We applied microarray technology to characterize gene expression of euthymic women with a history of PPD and compared the results with healthy controls. Our study demonstrated that women who considered euthymic on a clinical level, in fact, had an altered molecular profile when compared to participants with no PPD history. We identified nine genes significantly distinguished expression in post-depressive women; they may serve as a diagnostic tool for the detection of a predisposition to PPD.  Our findings contribute significantly to the understanding of PPD etiology and its pathogenesis, offer a plausible explanation for the risk of the PPD recurrence, and may also contribute to clinical treatment.

Biography:

Kathleen Hefferon has completed her PhD from University of Toronto and postdoctoral studies from the Department of Food Sciences, Cornell University. She is the Fulbright Canada Research Chair of Global Food Security. She is currently on Faculty at Cornell University and is writing a second edition to her book “Biopharmaceuticals in Plants.” Kathleen has published in multiple research journals and has edited 6 books. Kathleen just completed as editor of an Encyclopedia on Food Security and Sustainability. Kathleen lives in Ithaca, New York with her husband and two children.

Abstract:

Cellulases and other cell wall degrading enzymes are currently being engineered with improved traits for application in the breakdown of lignocellulosic biomass. The majority of assays with these ‘designer’ enzymes have been carried out using synthetic substrates such as crystalline bacterial microcellulose (BMCC). The use of synthetic substrates may not reflect the actual action of these cellulases on real plants. In the following study, suspension cell walls from several plant species were examined as possible alternatives for synthetic cellulose substrates. The results suggest that isolated plant cell walls can be used to reproducibly assay for cellulase activity

Biography:

Andréia de Haro Moreno is Graduate at Pharmacy from Universidade Paulista (2000), master’s at Pharmaceutical Sciences (2003) and a PhD in Pharmaceutical Research and Development from São Paulo State University (UNESP) – Faculty of Pharmaceutical Sciences (2007). She is currently a professor at Padre Albino University Center (UNIFIPA). He has experience in the field of Pharmacy, with emphasis in Analysis and Control of Medicines, working mainly in the following subjects: physical-chemical and microbiological quality control, manipulation pharmacies, laboratories of quality control of medicines and cosmetics, evaluation of antimicrobial activity of plant extracts, drug extracts, drug interactions and drugs and medicines.

Abstract:

Medicinal plants and herbal extracts were currently used for the treatment of several diseases has been growing all around the world. However, knowledge about the cytotoxic potential of plant extracts is very important to ensure safety during use. The objective of this work was to carry out the preliminary phytochemical study and to evaluate the hemolytic cytotoxicity of the Brazilian plant species Garcinia brasiliensis (Mart.) and Croton urucurana (Baill.). Samples (leaves and stems, respectively) of G. brasiliensis and C. urucurana were obtained from APTA, Brazil. After drying at 40ºC until constant weight, samples were crushed and the alcoholic extracts at 20% (w/v) were prepared by the percolation technique. After solvent evaporation, preliminary phytochemical study was carried out through specific chemical reactions for secondary metabolites. The cytotoxicity assay was performed by the determination of hemolysis degree after exposure the diluted extracts (0.2, 0.4, 0.6, 0.8 and 1.0 mL) in sterile physiological solution at 37ºC for 30 minutes in physiological suspension of red blood cells. The preliminary phytochemical study confirmed the presence of secondary metabolites, mainly polyphenols of the tannin and flavonoid classes. In the hemolytic cytotoxicity assay, the hemolysis was classified as low (20%) for both extracts at the concentrations tested. The results confirmed the presence of secondary metabolites, particularly polyphenols, as well as the low cytotoxic potential of the ethanolic extracts analyzed. Thus, the results indicate that the plants analyzed in this study may be promising and contribute in the future to obtain new therapeutic agents.

Biography:

Abstract:

Dolichol phosphate mannose synthase (DPMS), a GT-A folded 32kDa endoplasmic reticulum (ER) resident protein essential for the elongation of Man₅GlcNAc₂-PP-Dol to Man₉GlcNAc₂-PP-Dol, a precursor for Glc₃Man₉GlcNAc₂-PP-Dol (lipid-linked oligosaccharide, LLO) in asparagine-linked (N-linked) protein glycosylation.  Presence of several motifs (i.e., DXD, PKA, etc.) in the amino acid sequence makes DPMS susceptible to regulation while sensing environmental, metabolic and genetic challenges.  It responds to cAMP-mediated extracellular signaling by being phosphorylated.  The result is increase in DPMS catalytic activity which then serves as a driving force for enhancing the LLO synthesis and consequently the protein N-glycosylation due to a cross-talk involving DPMS, GlcNAc-1 phosphate transferase and Glc-P-Dol synthase.  The outcome is increased cellular proliferation.  Overexpression expression of the DPMS gene can independently mimics this process.  On the other hand, cells deficient in PKA due to mutation or removal of the phosphorylation site by site-directed mutagenesis makes them impaired to cAMP signaling.  Genetic deficiency of DPMS has been found in patient with congenital disorder of glycosylation (CDG) Type Ie.   

Inhibiting GlcNAc-1phosphate transferase with the protein N-glycosylation inhibitor tunicamycin reduces the DPMS catalytic activity in a time-dependent manner.  The result is development of ER stress due to accumulation of non- or under-glycosylated proteins in the ER lumen causing interference with the cell cycle transcriptional machinery followed by the cell cycle arrest.  The end point is activation of cellular suicide (i.e., programed cell death/apoptosis) by unfolded protein response (upr) signaling.  

Biography:

JM-Maixent received his Ph.D. from Paris VII University in 1987 at the INSERM. He did preclinical research work at the Procter & Gamble pharmacological Inc. in the cardiovascular domain.. Now his group is focussed on complementary and alternative medicine from foods and plants, with experimental research on membrane Na,K-ATPase interactions such as PUFA and cholesterol. He is currently the Editor-in-Chief of Cellular and Molecular Biology and expert at the ANSES (french food agency) in different committees (processing aids, food additives, novel foods, food material contact, chemical risk and water safety). His research is focussed on nutritional plants at the laboratory of the University « Université du Sud Toulon-Var, IAPS, Equipe Emergeante, 83957 La Garde ». He is authored of 82 original papers (Peer-reviewed publications), > 230 communications, >30 expertise’s reports with  >300 scientific opinions with AFSSA-ANSES (in the domains of additives, processing aids, novel foods, chemical risk, nutrition and water safety).

Abstract:

The first definition of food supplements in France was established by the decree 96-307 on April, 10th, 1996. The founding directive for food supplements adopted in 2002, (European Directive 2002/46/CE June, 10th, 2002) was transposed in France by the 2006-352 decree of March 20th, 2006 in France. This EU regulation permits the use of ingredients that are designed to physiology with a declaration of the products to the DGCCRF (General Direction for the competition, consumption and fraud prevention) prior to its commercialization. A scientific review could be added by the French food agency (Anses). From 2006 when the regulation was adopted until now there have been very limited number of approvals (261/2058 rejections). Vitamin and mineral claims were approved automatically, without any new clinical trials.  A list of all the ‘on hold’ claim ID numbers can be found on  http://ec.europa.eu/nuhclaims/resources/docs/cl aims_pending.pdf. The european agency for food (EFSA), published useful guidances (see EFSA’s general scientific guidance on health claim applications) and for botanicals the Regulatory Fitness and Performance program (REFIT). In conclusion, food supplements are one of the more regulated but the challenge is to have EU approved health claims with the objective to have enough safety and clinical evidences and cellular mechanism of action for food supplements. Thoughts and examples on food supplements safety and health calims will be discussed.

 Keywords: nutrition, regulation, health claims, food supplements

Biography:

Gonçalves is professor at Padre Albino University Center, Catanduva, São Paulo, Brazil (UNIFIPA). Currently he is a PhD student at Gynecology Department – UNIFESP (Federal University of São Paulo) He is interested in molecular mechanisms in breast reconstruction

Abstract:

Invasive breast cancer is the most common gynecological neoplasia among women and its late diagnosis leads patients to undergo radical mastectomy. A common complication in the flap is arterial ischemia and/or venous congestion. Hyperbaric therapy is an interesting strategy to obtain better vascularization and consequently the survival of the flap. Materials and methods: We were performed the surgery technique 30 rats were divided into 3 groups: 10 rats in the control group (5 rats with arterial ischemia and 5 rats with venous congestion), 10 rats with arterial ischemia and 10 rats with venous congestion. Each rat was anesthetized with 30 mg / kg of injected phenobarbital and underwent surgery to produce cutaneous tissue, following a technique described by Matsumoto (2017). Rats undergoing hyperbaric therapy performed a 90 minute per session, once a day, for 7 days. The evaluation of the vitality of the flap occurred on day 7. Necrosis area, ??inflammatory infiltration area and number of blood vessels were evaluated. Results: The venous congestion flaps had a smaller area of tissue necrosis compared to the flaps with arterial ischemia, by histological analysis. The same was observed in relation to the percentage of inflammatory infiltrate. The number of blood vessels was also higher in the venous congestion flaps. Conclusion: It was possible to demonstrate, in a preliminary way, that the hyperbaric therapy associated with the skin flap technique with arterial congestion has a better effect on tissue regeneration.

Key words: Hyperbaric therapy, flap ischemia, flap congestion, breast reconstruction.

Biography:

Ana Laura Martins de Andrade is a fourth year PhD student Physioterapy student at the Federal of University São Carlos. She received a bachelor’s degree in Physioterapy from Federal of University Alfenas and a master’s degree in Physiotherapy from Federal University São Carlos. Developed part of his doctorate at 3B's Research Group, University of Minho, Portugal. Her research interests include photobiomodulation, tissue engineering and stem cells therapy

Abstract:

Regenerative medicine and tissue engineering research as evolved extensively in the past few years based on the discovery of the use of mesenchymal stem cells (MSCs). The literature has sought alternatives how photobiomodulation (PBM) to increase proliferation and still maintain the stem cells characteristics however, the large discrepancy between parameterization impairs the comparison among studies besides the mechanisms involved in PBM have not yet been clarified. Thus, this study aimed to explore the PBM action in different levels of energy, on the behavior of hASCs in 2D anda 3D conditions. The hASCs were isolated from human subcutaneous tissue samples obtained from liposuction. We used a red laser, (InGaAIP) with wavelength of 660 nanometers (nm), power of 40 mW and energies of 1 J, 2 J e 6 J. Analyzes of cytotoxicity and cell viability, cell proliferation and oxidative stress were performed.The evaluations showed that the energies of 1 J and 2 J were more effective for cell proliferation, and an inhibitory action was observed with energy of 6 J. In addition, PBM has been shown to have direct action on oxidative stress (ROS). According to the data presented, we concluded that PBM (660nm) is efficient in hADSCs proliferation modulating ROS.

Acknowledgments: Fundação de Amparo à Pesquisa do Estado de São Paulo (2015/17648-9)

Keywords: photobiomodulation; three-dimensional cultures; stem cells.

Biography:

Tarek Mohamed Kamal Mohamed Metawie, Professor of Biochemistry, Faculty of Pharmacy, Cairo University. Egyptian, date of birth 6/3/1955. Ph.D. in Pharmaceutical Sciences, 1984; M.Sc. in Pharmaceutical Sciences, 1979; B.Sc. in Pharmaceutical Sciences, Faculty of Pharmacy, Cairo University, 1976.

Abstract:

Paracetamol and diclofenac are two of the most popular analgesics and anti-inflammatory medications. Despite of their several therapeutic benefits, their over consumption led to subsequent cellular damage. Their cytotoxicity is attributed to reactive radical generation. Betanin has antioxidant and anti-inflammatory properties. The protective effects of betanin against paracetamol or diclofenac induced neurotoxicity or endocrine disruption has not been investigated before. Therefore, this study aims to explore the protective potential of betanin against paracetamol or diclofenac neurotoxicity and endocrine disruption in a rat model. In brain, paracetamol (400 mg/ kg) and diclofenac (10mg/kg) enhanced DNA fragmentation and lipid peroxidation level. A depletion of GSH content concomitant with a reduction in the activities of antioxidant enzymes (HOX-1, POX-1, CAT and SOD) were detected. Serotonin, nor-adrenaline and dopamine levels were markedly reduced after paracetamol and diclofenac challenge. In serum, a significant reduction of testosterone, TRH, TSH, T₃ and T₄ were associated with the enhanced oxidative damage. Co-treatment of rats with betanin (25mg/kg) by gavage for 28 consecutive days ameliorated most of the biochemical and histopathological changes induced by paracetamol or diclofenac. In conclusion, betanin exerted a potential chemomodulatory effect against paracetamol or diclofenac overconsumption induced neurotoxicity and endocrine disruption.

Biography:

Mahmoud samy is a first-year administration student at the University of 6th October School of Pharmacy. He received a bachelor’s degree in pharmaceutical sciences from 6th October  University. His current field placement is with the researches and education. His research interests include inflammation, Antioxidant Activity, Oxidative Stress, Signaling Pathways, Clinical Chemistry.

Abstract:

MicroRNA 26a (Mir-26a) reported to modulate gene regulation influences the maintenance of metabolic homeostasis, particularly the states of obesity, thereby providing a potential link between miRNAs and nonalcoholic fatty liver disease (NAFLD). Methods: In the current study, experimental rats were fed a high-fat diet (HFD) for 6 and 16 weeks to establish a rat model of NAFLD, while control rats received standard chow. Serum and liver tissue was collected from all animals at 6 and 16 weeks of feeding. Biochemical parameters (cholesterol, TG, AST, ALT, NEFA) were determined. Hepatic lipid accumulation was estimated by Oil red O staining. Vectors encoding pre-Mir-26a (LV-26a) and an empty lentiviral vector (LV-Con) were injected to mice through the tail vein. Serum IL-6 was measured by ELISA and miR-26a was detected by qRT-PCR. Results: Over the 16 weeks of feeding, body weight, liver lipids, serum triacylglycerol levels and ALT, AST aminotransferases activities were markedly elevated in the HFD group compared to the control group. In contrast, LV-26a-infected mice showed marked reduction of total liver weight, hepatic triglyceride deposition and serum ALT concentration when compared with LV-Con-treated mice. In addition, the in vitro experiments with HepG2 and Huh7cells showed that mir-26a inhibits the expression of IL-6. Furthermore, histopathological examination of hepatic tissue reinforced these results.  Conclusion: Our findings suggest that mir-26a-IL-6 axis regulates the development of NAFLD in a rodent model. Therefore, serum miR-26a level is indeed useful for assessing early NAFLD and might be superior to clinical markers traditionally used to monitor hepatic disease.

Keywords: Mir-26a; IL-6; NAFLD, HepG2 cells