15^th International Conference and Exhibition on Nanomedicine and Pharmaceutical Nanotechnology March 18-19, 2019 HOLIDAY INN PARIS - PORTE DE CLICHY

Biography:

Shuntaro Hara received his MS and PhD degree’s from the University of Tokyo and started his research career as a Post-doctoral fellow at the University of Tokyo. After postdoctoral training, he worked as a Research Associate at the National Cardiovascular Center Research Institute (Osaka, Japan) and as a visiting Fellow at University College London. He also worked as an Assistant Professor at Kitasato University (Tokyo, Japan), and then he became Professor at the School of Pharmacy, Showa University in 2009. He has published more than 100 papers in reputed journals.

Abstract:

Acyl coenzyme A synthetase long-chain family members (ACSLs) are a family of enzymes that convert long-chain free fatty acids into their acyl-CoAs. Among ACSL isozymes, ACSL4 has been hypothesized to modulate the metabolic fates of polyunsaturated fatty acids including arachidonic acid. In the present study, to investigate the enzymatic and protein characteristics of ACSL4, the cDNA for human ACSL4 was cloned from human epithelial colorectal adenocarcinoma Caco-2 cells and then recombinant ACSL4 enzyme containing a C-terminal His-tag was expressed in Spodoptera frugiperda 9 (Sf9) cells using the baculovirus expression system. ACSL4 enzyme activity was detected in 10,000xg supernatants of ACSL4-expressing Sf9 cell lysates and then partially purified by nickel affinity column chromatography. We further investigated the substrate specificity of recombinant human ACSL4 by LC/MS and found that ACSL4 enzyme preferred various kinds of polyunsaturated fatty acids including docosahexaenoic acid, docosapentaenoic acid, eicosopentaenoic acid, and dihomo-γ-linolenic acid, as well as arachidonic acid as a substrate. On the other hand, oleic acid, linoleic acid and linolenic acid were poor substrates, although these fatty acids contain unsaturated bonds. These results confirmed the importance of ACSL4 in maintenance of membrane phospholipid bearing polyunsaturated fatty acid.

Biography:

Ina Buchholz has studied Biochemistry at the University of Greifswald, with main focus on Analytical Biochemistry and Biophysics. Currently, she is a PhD student in the group of Prof. Mihaela Delcea at ZIK HIKE (Center of Innovation for Humoral Immune Responses in Cardiovascular Disorders). She investigates blood- and non-blood proteins involved in autoimmune diseases and the impact of environmental factors (e.g. pH, ionic concentrations, and temperature), mutations and post-translational modifications on protein structure and immunogenicity.

Abstract:

Beta2-glycoprotein I (beta2GPI) is a soluble blood protein (326 AA, five domains) exhibiting two main conformational states: the circular or closed conformation, where the first domain (DI) is bound to the last domain (DV) of the protein; and the linear or open conformation. In the open form, beta2GPI binds to phospholipid membranes via DV and this form is considered to play a crucial role in the autoimmune disease antiphospholipid syndrome (APS). Therefore, investigating the structural dynamics of this protein is of high interest. We investigated different post-translational modifications (PTM) of beta2GPI and studied the impact on its conformation with biophysical tools (e.g. atomic force microscopy, circular dichroism spectroscopy). Additional insights into the interaction of DI and DV were gained from molecular dynamic simulation studies. PTM 1: Lysine residue acetylation reveals a partial opening of beta2GPI dependent on the acetylation ratio used (Buchholz et al., PCCP 2018). These data indicate that lysines predominantly stabilize the closed conformation and in vivo acetylation via acetyltransferases could destabilize the closed form, leading to a facilitated opening of the structure. PTM 2: Enzymatic reduction of the C-terminal Cys288/Cys326 disulfide bond near the putative contact interface of DI and DV also initiates a conformational change of beta2GPI. Furthermore, disruption of this disulfide bond leads to loosening of a 22 AA flexible loop carrying lysine residues critical for phospholipid membrane binding. In summary, these PTM reveal a critical level of destabilization of the closed beta2GPI conformation and beta2GPI conformational change may have a large impact on APS disease.

Biography:

Payal Ghosh has pursuing her MS from University of South Florida from College of Pharmacy. She has completed her Bachelor’s degree in Pharmacy from India. Then she worked as a Marketing Manager in a pharmaceutical company. She wants to work on neurological disorder in upcoming future.

Abstract:

The prevalence of neurodegenerative disorders has dominated humankind throughout history. Huntington’s disease (HD) is a prime example in this category. Statistical data shows that every seven to eight people out of 100 are affected by this disease in Western countries. HD causes brain retardation, dementia, and slow movement of limbs and in extreme the death, all of which is primitively caused by damage in brain cells. Though HD is well known, mostly only genetic treatments have been performed till date. Whereas an insufficient production of thyroid hormones can lead to death of brain cells, which results in the occurrence of brain diseases. Dietary iodine acts on thyroid gland and produces the T₃ (triiodothyronine) and T₄ (thyroxine) to nourish the brain cells, which will prevent the death of brain cell simultaneously the HD. Bilayer lipid coated iodine nanoparticle (outside) along with T₃ and T₄ (inside) will be administered to the brain. The MCT8 transporter (monocarboxylate 8 transporter) which transports T₃ and T₄ to the brain will be coated outside of this bi-layer nano-particle. Scanning electron microscopy (SEM) and fluorescence spectroscopy and in vitro analysis on animals will be the best analytical tools. The MCT8 layer will attach to the blood brain barrier (BBB) and makes easy passage for the nano-particle. Nano formulation of iodine acts on brain cell to stimulate its function which will prevent the death of brain cell thus it will slower down the occurrences of the HD. Iodine nanoparticle is a economical and easily available compound and can be used as a good therapeutic agent for HD. As there is no previous data available of the same it will be a great opportunity to investigate this, however, the toxicity level of iodine nanoparticles are still need to be investigated if administered for a long period of time.

Biography:

Ana Merino has completed her PhD at the University of Córdoba (Spain) and Post-doctoral studies at the Biomedical Institute of Bellvitge (IDIBELL) in Barcelona (Spain). She has published more than 30 papers in indexed journals. As a senior Researcher, she is currently developing the project: Pre-clinical evaluation of membranes particles from mesenchymal stem cells for immune and degenerative disorders. This project is being developed in the Internal Medicine department from Erasmus Medical Center (Rotterdam, The Netherlands) in collaboration with the company Takeda-Tigenix.

Abstract:

Mesenchymal stromal cells (MSC) are studied as an immunomodulatory and regenerative therapy in organ repair. Recent work demonstrated that dead MSC which are unable to secret factors, are effective in a sepsis model, suggesting that MSC activity is dependent on the cell membrane interactions with immune cells. We propose a new therapy based on the generation of plasma Membrane Particles (MP) from MSC. We previously showed that MP were effective in reducing the inflammatory phenotype of monocytes. In this study, we investigated the therapeutic potential of MP as regenerative treatment for EC in a TNF-α inflammatory condition. MP were generated from MSC by hypotonic shock and extrusion. MP showed vesicle shape (cryoelectron-microscopy) and a size below 200 nm. Uptake of MP by EC was analyzed by confocal microscopy, and within 24 hours >90% of EC have taken up MP. Three different concentrations of MP were tested on EC. None of the MP concentrations induced apoptosis or activation of EC measured by the expression of the adhesion markers such as ICAM-1, and VCAM. With respect to the regenerative capacity of EC after MP treatment, we have observed an enhancement of angiogenesis by increasing the number of tubes, and branches formation in vitro compared to the negative control (non-treated EC). In the scratch wound healing assays, MP had a stimulating effect on EC to fill the scratch in a dose-dependent manner. In conclusion, MP potentially serve as a novel cell derived therapy that restores vascular integrity and induces endothelial regeneration.

Biography:

Una Janke has studied Human Biology at the University of Greifswald, with the main focus on Immunology. Currently, she is a PhD student in the group of Prof. Mihaela Delcea at the Institute of Biochemistry and uses biophysical tools to investigate the impact of mutations and environmental factors (e.g. ions, drugs) on activation and immunogenicity of platelet receptor integrin αIIbβ3.

Abstract:

The transmembrane protein integrin alpha IIb beta 3 (αIIbβ3) is involved in hemostasis, wound healing and clot formation. Intracellular as well as extracellular signals can cause inside-out or outside-in signaling, which leads to atleast three different conformations: the bent (resting) state; the intermediate extended form; and the ligand-occupied active state. The conformational dynamics of the overall structure of αIIbβ3 during the activation process is possibly related to changes in protein secondary structure, which has not been studied until now in a membrane environment (e.g. liposomes). Moreover, αIIbβ3 is related to the autoimmune disease immune thrombocytopenia, where potential external triggers influence the antigenicity of the integrin by changing the protein structure. In this study, we determined the drug-induced activation of αIIbβ3 and the relation to the structure of this protein reconstituted into liposomes. The combination of activation assays and the biophysical tools quartz crystal microbalance, surface plasmon resonance and circular dichroism spectroscopy show binding of the conformation-specific antibody PAC-1 (which recognizes the active integrin) to αIIbβ3-treated with clinically relevant drugs (e.g. quinine). However, insignificant changes in protein secondary structure were found. Molecular dynamics simulation (MDS) studies confirmed a globular hinge motion in the ectodomain of the integrin with minor changes in protein secondary structure. Our biophysical setup in combination with MDS can be applied to study transmembrane proteins under different conditions in a biomimetic system.

Biography:

Perry Habib Saifullah,  I work in the department of Chemistry,  College of science for women,  University of Baghdad.  . The field of my research is based on the diagnosis,  prognosis and,  treatment of diabetes mellitus  patients.  I had supervised  my master and doctorate in the field of biochemistry,  and medical biochemistry  . I also work as a director for Career and development unit in my college and trying to improve the curriculum of our department  in a way that provides students with knowledge skills and soft skills.

Abstract:

Both Alzheimer’s disease (AD) and diabetes mellitus disorder share the most prevalence devastating healthy problems in the old people. Diabetic is a known as a risk factor for the emergence of cognitive dysfunction and dementia complication. Biological and epidemiological evidences confirmed a link between the two diseases, but the precise mechanisms that involved in the developing of cognitive impairment in diabetic patients are not fully comprehended. The Alpha -7 nicotinic acetylcholine receptors (α7-nAChRs) are a type of transmembrane ligand, that are activated through in response to the neurotransmitters such acetylcholine (ACh) and other agonist like nicotine. It belongs to superfamily of receptors that are the fast ionotropic cationic ligand-gate ion channels in nervous, and muscle cell tissues. This receptor play a vital role in the supporting the cognitive function of animal , learning and memory potency by the neurotransmission adjusting , through the control secretion of a different neurotransmitters. Several previous studies had been demonstrated, that the decline in nicotinic receptors mostly the (α-7nAchR) subtype are linked with aging, and also reduced particularly in brain AD patients. The current study included two aims, the first was the investigation about the abundance of (α-7nAchR) at the brain tissue of mice that induced diabetic disease conditions. Second aim was the study the influence of orally metformin drug (which considered as the first line treatment of diabetic disease type 2) on the (α-7nAchRs) abundance in brain tissue of treated diabetic mice by metformin during a therapy duration was 45 days, by means of using the technique detection, the immunohistochemistry (IHC).

Biography:

Eman A Bseiso is working as Assistant Lecturer in the Department of Pharmaceutics & Industrial Pharmacy, Faculty of Pharmacy, October 6 University in Egypt. She earned a Bachelor’s degree in Pharmaceutical Science in 2010 and Master’s degree in Phramaceutics from Faculty of Pharmacy, Ain Shams University in Egypt. Currently, she is pursuing her PhD in Pharmaceutical Technology, Faculty of Pharmacy from the same university. She has published many papers in reputed journals and her current research interests focuses on dermal & intranasal drug delivery systems by using polymers and surfactants to enhance the performance of the large and small drug candidates in addition to nanoparticle formulations for drug targeting (e.g. SLN, NLC & liposomes).

Abstract:

The objective of the current study was to assess the feasibility of nose to brain delivery of melatonin (MEL) using a lipidic nanocarrier (LNCs) for treatment of oxidative diseases. This carrier was chosen owing to its small size and biocompatible nature and is prepared using solvent-free phase inversion temperature technique. Design of experiment was used to establish D-optimal mixture design to study the impact of individual and combined effects of three independent variables; X1 (Oil), X2 (Surfactant), and X3 (Drug), on three LNCs responses; Y1 (particle size), Y2 (Polydispersity index) and Y3 (Zeta potential). MEL-LNCs were successfully prepared and characterized in terms of size, PDI and zeta potential. In-vitro drug release profiles and viscosity were assessed for the optimized LNCs. Results showed that all LNCs had a particle size ranging from 20-200 nm which was appropriate for intranasal permeability and brain targeting. They mostly exhibited narrow size distribution and a negative charge. They also exhibited a sustained release behavior. LNCs were shown to be a promising delivery system for possible nose to brain delivery of MEL.

Biography:

Abstract:

Background: Methotrexate is a systemic immunosuppressant drug that is used for the treatment of psoriasis and psoriatic arthritis. Previous studies demonstrated a potential association between psoriasis and diabetes mellitus, obesity, atherosclerosis and hypertension.

Objective: This study aimed at exploring the possible hyperglycaemic effects of methotrexate in psoriatic arthritis patients (PsA).

Methods: In this prospective cross-sectional study, 27 patients with PsA were evaluated. The status of PsA and presence of accompanying metabolic syndrome was determined by standard criteria and indexes. Blood indicators including, HbA1c, erythrocyte sedimentation rate (ESR), fasting blood sugar (FBS), total cholesterol, high-density lipoprotein (HDL), triglycerides, and C-reactive protein (CRP) were examined before and 12 weeks after methotrexate therapy.

Results: There were no significant changes between HbA1c levels before and after methotrexate therapy in both genders (men: P= 0.131, women: P=0.803). In addition, HbA1c levels in PsA patients with metabolic syndrome were not different before and after treatment (P=0.250). Finally, HbA1c levels did not change in PsA patients without metabolic syndrome before and after therapy (P=0.506).

Conclusion: Methotrexate in PsA patients does not appear to have hyperglycaemic effects in the short-term and can be safely used in patients with metabolic syndrome and diabetes.

Biography:

Abstract:

Biography:

Angie Andrea Bedoya Rodríguez has completed her MSc in Biochemistry and currently is a PhD student in Biotechnology at National University of Colombia. The current work belongs to her thesis topic.

Abstract:

Oncolytic virus therapy is a breakthrough in cancer treatment. Rotavirus is the leading cause of gastroenteritis and a large part of the population has immunological memory against it. Therefore, it is necessary to look for a biomaterial that permits shielding of WT1-5 oncolytic rotavirus in order to elude the antibody recognition and reach the tumor satisfactorily. For this, we used red blood cells (RBC), peripheral blood mononuclear cells (PBMC) or platelets as potential oncolytic rotavirus carriers. To encapsulate or bind virus to these cells, WT1-5 was incubated with cationic polyelectrolytes (polybrene, and protamine) or heparin and the formed nanocomplex (virus-polymer) was added to RBC, PBMC or platelets. RBC, PBMC or platelets loaded with WT1-5 were co-cultured with tumor cells (SK-MEL 28 or MCF-7) to evaluate the infection. Likewise, the release of rotavirus bound or encapsulated in RBC, PBMC or platelets at different times was evaluated, for this, the loaded cells were incubated every 30 min, centrifuged and the supernatant was recovered, which was added to the tumor cells. RBC loaded with WT1-5, by means of polybrene, increased the infection of tumor cells more than threefold with respect to positive control (WT1-5 incubated directly with tumor cells). With PBMC and platelets, similar results were obtained. We used another method, RBC-derived purified membranes or RAFTs-coated rotavirus WT1-5, which was added to tumor cells to evaluate infection. Both effectively coated rotavirus WT1-5, kept in suspension (carry), avoided antibody recognition, and allowed the infection of the tumor cells. Peripheral blood cells are promising cell carriers for efficient delivery of WT1-5 oncolytic rotavirus. Currently, we are also developing nanocomplexes between the rotavirus and alginate gel matrix system yielding good results.

Biography:

Angie Andrea Bedoya Rodríguez has completed her MSc in Biochemistry and currently is a PhD student in Biotechnology at National University of Colombia. The current work belongs to her thesis topic.

Abstract:

Oncolytic virus therapy is a breakthrough in cancer treatment. Rotavirus is the leading cause of gastroenteritis and a large part of the population has immunological memory against it. Therefore, it is necessary to look for a biomaterial that permits shielding of WT1-5 oncolytic rotavirus in order to elude the antibody recognition and reach the tumor satisfactorily. For this, we used red blood cells (RBC), peripheral blood mononuclear cells (PBMC) or platelets as potential oncolytic rotavirus carriers. To encapsulate or bind virus to these cells, WT1-5 was incubated with cationic polyelectrolytes (polybrene, and protamine) or heparin and the formed nanocomplex (virus-polymer) was added to RBC, PBMC or platelets. RBC, PBMC or platelets loaded with WT1-5 were co-cultured with tumor cells (SK-MEL 28 or MCF-7) to evaluate the infection. Likewise, the release of rotavirus bound or encapsulated in RBC, PBMC or platelets at different times was evaluated, for this, the loaded cells were incubated every 30 min, centrifuged and the supernatant was recovered, which was added to the tumor cells. RBC loaded with WT1-5, by means of polybrene, increased the infection of tumor cells more than threefold with respect to positive control (WT1-5 incubated directly with tumor cells). With PBMC and platelets, similar results were obtained. We used another method, RBC-derived purified membranes or RAFTs-coated rotavirus WT1-5, which was added to tumor cells to evaluate infection. Both effectively coated rotavirus WT1-5, kept in suspension (carry), avoided antibody recognition, and allowed the infection of the tumor cells. Peripheral blood cells are promising cell carriers for efficient delivery of WT1-5 oncolytic rotavirus. Currently, we are also developing nanocomplexes between the rotavirus and alginate gel matrix system yielding good results.

Biography:

Samia Bouledoua, Research Professor in Mineral Chemistry at the Faculty of Medicine, Université BADJI Mokhtar .Annaba (Algeria), is currently working on her PhD in Nanoscience and Nanotechnology

Abstract:

The nanoparticles have attracted great interest due to their unique physical and chemical properties, and zinc oxide (ZnO) is one of metal oxide nanoparticles, which attracts considerable attention due to its unique characteristics and its wide range of important technological applications. Nanocomposites are characterized by a combination of inorganic materials in the same particle. These assemblies have properties ranging from those of each of the constituents. The properties of ZnO nanoparticles can be improved depending on the interest of doping research with different metal atoms to meet specific needs and applications. Therefore, doping in the host matrix of zinc oxide nanoparticles with appropriate elements can adjust different properties of ZnO and is an effective method for improving and controlling its properties, which is crucial for its practical applications. Mg-doped ZnO is of considerable interest because of its unique optical, electrical and piezoelectric characteristics. Our work consists in the synthesis of a ZnO / Mg nanocomposite by a chemical coprecipitation method. The characterization of the synthesized nanocomposite was determined by X-ray diffraction (XRD) and UV-visible spectrophotometry. The DRX, on the one hand, makes it possible to determine the crystalline structure of the nanocomposite which is of wurtzite type, and secondly to calculate the size of crystallites obtained by the application of the Scherrer equation in the diameter of 49.44 nm. The UV visible spectrophotometry meanwhile revealed the existence of a maximum absorbance at 372 nm and allowed to assert that the synthesized powder corresponds to ZnO / Mg nanocomposites.

Biography:

Oznur Aglar has completed her Master’s degree in Organic Chemistry at Umea University, Sweden, in 2016. She is currently a second-year PhD doctoral student in Analytical Chemistry at the University of Potsdam. Her current research focuses on the study of protein-ligand interactions, including binding affinity and binding kinetics by NMR.

Abstract:

Ceramide, an important component in the metabolism of sphingolipids, plays a significant role in proliferation, and apoptosis of cells. De novo synthesis of ceramide takes place at the cytosolic surface of the endoplasmic reticulum (ER), and then, ceramide is transferred to the Golgi apparatus for conversion into sphingomyelin and glucosphingolipids, mainly by nonvesicular trafficking. Non-vesicular transport of ceramide is carried out by the ceramide transfer protein (CERT) that consists of peptidic motifs and multiple domains. The C-terminal (StAR)- related lipid transfer (START) domain is the most important domain given the fact that it is capable of extracting and accommodating ceramide in its deep hydrophobic cavity. CERT could be an attractive pharmacological target because of its involvement in common pathological processes such as Alzheimer's disease, infectious diseases and cancer. A well-known antagonist of CERT is -N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl) dodecanamide (HPA-12), however, there is only limited structure-activity relationship (SAR) data available. In this study, we aim to explore the interaction between CERT and HPA-12 to establish SAR of this compound class by nuclear magnetic resonance spectroscopy (NMR) in order to improve the inhibition activity of the ligand for a potential drug design. Herein, we optimized the established expression and purification protocols to get a good yield of the monomer of the START domain. In order to get an idea about the suitability of the protein of interest for ligand and receptor-based NMR experiments, the target protein was labeled with 15N and purified using an optimized three step purification method. The 15N labeled START domain’s monomer was used to record initial 1H - 15N HSQC and TROSY NMR spectra in phosphate buffer. Results of both HSQC and TROSY experiments were promising for further receptor based NMR experiments.

Biography:

Abstract:

Background: Silver colloids, silver nanoparticles suspended in liquid exposure properties Chemical, optical and antimicrobial materials widely used in a wide field of application. For these antibacterial and antifungal and antiviral qualities, psoriasis and eczema, these Specific properties are heavily influenced by particle size and shape. The methodology of the experiments plans is an optimal strategy allowing to organize the tests which accompany. A scientific research allows it to obtain the maximum of information with a maximum of precision from a minimum number of experiments in the fastest time and for the least cost[1] Our work consists in successfully synthesizing a colloidal solution of silver nanoparticles with the use of nitrate of silver as precursor and sodium citrate as reducing agent and optimizes the operating conditions. Materials & Methods: thermometer for solution, centrifuge, Analytical Balance, UV-spectrophotometer. [2] Observations: It should be noted that the process of formation and growth of nanoparticles can be easily affected by a multitude of factors, all the glassware must be cleaned by a solution of aqua regia. Results: The field of study allows to synthesize colloids whose mean particle size varies between 59.22nm and 111.85nm. Discussion: A change in the concentration of citrate in the colloid has an effect on the rate of reduction and on the nucleation / growth ratio. [3] Conclusion: synthesis of a silver colloid by chemical reduction using silver nitrate as a precursor and sodium citrate is easy to achieve.

Biography:

Alaimo A is a Young Assistant Researcher at the National Scientific and Technical Research Council (Spanish: Consejo Nacional de Investigaciones Científicas y Técnicas, CONICET), the Argentine government agency, which directs and co-ordinates most of the scientific and technical research done in universities and institutes. She is a highly motivated and innovative Cellular and Molecular Biologist with specialization in Mitochondria biology, Molecular genetics, Cell biology, Biochemistry and Nanotechnology. She is an enthusiastic team player adept at providing leadership, while also learning from fellow team members.

Abstract:

Age-related macular degeneration (AMD) is a progressive retinal disease and is the leading cause of visual impairment in elderly people in western countries, for which there is still no cure. Genetics, environmental insults, and age-related issues are risk factors for the development of the disease and all these are linked to oxidative stress induction. Also, degeneration of retinal pigment epithelial cells (RPE) is a crucial causative factor responsible for the onset and progression of AMD. With the population aging, AMD will gradually become in a globally prevalent disease. The decline in the quality of life among affected patients highlights a critical need for developing preventive strategies. In this sense, phytochemicals with both antioxidant and anti-inflammatory properties may have a potential role in the prevention and treatment of this ocular disease. Particularly, there is an increased interest in the therapeutic effects of resveratrol (RSV). RSV is a naturally occurring polyphenolic compounds from the stilbenes family, mainly found in black grape and peanuts. RSV has beneficial effects on human health, including its neuroprotection, anti-inflammatory action, potent antioxidant activity and antiaging effects. Our research line is focused in investigating the protective effectiveness of RSV in an in vitro model of AMD. In addition, we designed and developed chitosan-based nanocarriers for RSV encapsulation to overcome physicochemical and pharmacokinetic limitations such as poor oral bioavailability, low water solubility and photosensibility. In summary, chitosan nanoparticles are a promising platform for ocular bioactives (eg. RSV) delivery for therapeutic intervention against oxidative stress-associated diseases, such as AMD