Search results for: tPA inhibitor

Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

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Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

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Authors: Ji-Seok Hong, Hee-Jang Moon, Hong-Gye Sung

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The details of flow structures and the coupling mechanism between vortex shedding and acoustic excitation in a solid rocket motor with two inhibitors have been investigated using 3D Large Eddy Simulation (LES) and Proper Orthogonal Decomposition (POD) analysis. The oscillation frequencies and vortex shedding periods from two inhibitors compare reasonably well with the experimental data and numerical result. A total of four different locations of the rear inhibitor has been numerically tested to characterize the coupling relation of vortex shedding frequency and acoustic mode. The major source of triggering pressure oscillation in the combustor is the resonance with the acoustic longitudinal half mode. It was observed that the counter-rotating vortices in the nozzle flow produce roll torque.

Keywords: large eddy simulation, proper orthogonal decomposition, SRM instability, flow-acoustic coupling

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Authors: Ahmed Malki

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Breast cancer has been identified as the most lethal form of cancer today. In our study, we designed and screened 16 steviosides derivatives for their cytotoxic activities in MCF-7human breast cancer cells and normal MCF-12a cells. Our data indicated that steviosides derivatives 9 and 15 decreased cell proliferation and induced apoptosis in MCF-7 breast cancer cells more thannormal breast cells epithelial cells. Flow cytometric analysis showed that both steviosides, derivatives 9 and 15 arrested the MCF-7 cells in G1 phase, which is further confirmed by the increased expression level of p21. Moreover, both steviosides derivatives increased caspase-9 activity, and the induction of apoptosis was significantly reduced after treating cells with caspase-9 inhibitor LEHD-CHO. Both steviosides derivatives increased Caspase 3 activities and induced Parp-1 cleavage in H1299 cells. Based on previous results, we have identified two novel steviosides derivatives which provoked apoptosis in breast cancer cells by arresting cells in G1 phase and increasing caspase-9 and caspase-3 activities which merits further development and investigations.

Keywords: steviosides, breast cancer, p53, cell cycle

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Authors: Jung-Feng Hsieh, Chu Ze Chen

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Curcumin is the main active compound of turmeric that can inhibit the activities of α-glucosidase and xanthine oxidase (XO). α-Glucosidase and XO inhibitors are widely used to treat patients with diabetes mellitus and gout, respectively; therefore, the objective of this research was to evaluate the inhibitory activities of curcumin and its analogs against α-glucosidase and XO. Our results demonstrated that CM-F had the strongest antioxidant activity with a half-maximal effective concentration (EC50) of 9.39 ± 0.16 μM, which was superior to vitamin E (EC50=17.03 ± 0.09 μM). CM-F also exhibited potent inhibitory activity against XO with an IC50 value of 6.14 ± 0.38 μM and enzyme kinetic results revealed competitive inhibition of XO. We also found that CM-1 and CM-2 inhibited α-glucosidase with IC50 values of 21.06 ± 0.92 μM and 5.95 ± 0.09 μM, respectively, and kinetic studies indicated that both CM-1 and CM-2 are mixed competitive inhibitors of α-glucosidase. Furthermore, docking simulation identified five hydrogen bonds between XO and CM-F; however, only one and two hydrogen bonds are involved in CM-1 and CM-2 binding to α-glucosidase, respectively. Accordingly, curcumin and its analogs have the potential to be used in the treatment of patients with diabetes mellitus and gout.

Keywords: curcumin, α-glucosidase, inhibitor, xanthine oxidase

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Authors: Ghazala Yaqub, Zubi Sadiq, Almas Hamid, Saira Iqbal

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This paper is the very first report of three dual action hybrids synthesized by covalent linkage of carbazole based novel antibacterial compounds with efflux pump inhibitors i.e., indole acetic acid/gallic acid. Novel carbazole based antibacterial compounds were prepared first and then these were covalently linked with efflux pump inhibitors which leads to the successful formation of hybrids. All prepared compounds were evaluated for their bacterial cell killing capability against Escherichia coli, Staphylococcus aureus, Pasteurella multocida and Bacillus subtilis. Compound were effective against all tested bacterial strains at different concentrations. But when these compounds were linked with efflux pump inhibitors they showed dramatic enhancement in their bacterial cell killing potential and minimum inhibitory concentration of all hybrids ranges from 7.250 µg/mL to 0.0283 µg/mL.

Keywords: antimicrobial assay, carbazole, dual action hybrids, efflux pump inhibitors

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Authors: Khaled Khleifat, Muayyad Abboud, Ahmad Almustafa

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The effect of metabolic inhibitor/uncoupler(s) (CCCP and NaN3) and sulfhydryl reagents (dithiothreitol, 2 mercaptoethanol glutathione) on cadmium uptake was investigated in Enterobacter aerogenes strains. They include a transformed strain bearing the Vitreoscillahemoglobin gene, vgb as well as control strains that lack this transformed gene. The vgb-harboring strains showed better uptake of cadmium than vgb-lacking strains. Under low aeration, there was 2 fold enhancement of Cd+2 uptake in vgb-harboring strains compared with 1.6-fold enhancement under high aeration. The CCCP caused 36, 40 and 58% inhibition in cadmium uptake of parental, pUC9 harboring and VHb expressing cells, respectively. Similarly, the sodium azide exerted 44, 38 and 55% inhibition in Cd+2 uptake of parental, pUC9 harboring and VHb expressing cells, respectively. Less extensive inhibition of Cd+2 uptake in the range of 11 to 39% was observed with sulfhydryl reagents.

Keywords: bacterial hemoglobin, VHb, Cd uptake, biosorption

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Authors: Nisrine Benzbiria, Mohammed Azzi, Mustapha Zertoubi

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2XXX series of aluminum alloys are widely employed in several applications, such as beverages, automotive, and aerospace industries. However, they are particularly prone to localized corrosion, such as pitting, often induced by a difference in corrosion potential measured for intermetallic phases and pure metal. The galvanic cells comprising Al–Cu– Mn–Fe intermetallic phases control cathodically the dissolution rate as oxygen reduction reaction kinetics are privileged on Al–Cu–Mn–Fe particles. Hence, understanding the properties of cathode sites and the processes involved must be carried out. Our interest is to outline the cathodic behavior of AA2024-T3 in sodium sulfate solution using electrochemical techniques. Oxygen reduction reaction (ORR) was investigated in the mixed charge transfer and mass transport regime using the Koutecky-Levich approach. An environmentally benign inhibitor was considered to slow the ORR on the Cu-rich cathodic phases. The surface morphology of the electrodes was investigated with SEM/EDS and AFM. The obtained results were discussed accordingly.

Keywords: AA2024-T3, neutral medium, ORR kinetics, Koutecky-Levich, DFT

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Authors: Rafayel Azizyan, Valeri Arakelyan, Aram Gevorgyan, Varduhi Balayan, Emil Gevorgyan

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Currently, mathematical and computer modeling are widely used in different biological studies to predict or assess behavior of such complex systems as biological ones. This study deals with mathematical and computer modeling of bi-substrate enzymatic reactions, which play an important role in different biochemical pathways. The main objective of this study is to represent the results from in silico investigation of bi-substrate enzymatic reactions in the presence of uncompetitive inhibitors, as well as to describe in details the inhibition effects. Four models of uncompetitive inhibition were designed using different software packages. Particularly, uncompetitive inhibitor to the first [ES1] and the second ([ES1S2]; [FS2]) enzyme-substrate complexes have been studied. The simulation, using the same kinetic parameters for all models allowed investigating the behavior of reactions as well as determined some interesting aspects concerning influence of different cases of uncompetitive inhibition. Besides that shown, that uncompetitive inhibitors exhibit specific selectivity depending on mechanism of bi-substrate enzymatic reaction.

Keywords: mathematical modeling, bi-substrate enzymatic reactions, reversible inhibition

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Authors: C. R. Stein; K. Skeff Neto, K. L. C. Miranda, P. P. C. Sartoratto, M. E. Xavier, Z. G. M. Lacava, S. M. De Freita, P. C. Morais

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In this study, static magnetic birefringence (SMB) and transmission electron microscopy (TEM) were used to investigate the self-assembling of maghemite nanoparticles suspended as biocompatible magnetic fluid (BMF) while incubated or not with the Black Eyed–Pea Trypsin Chymotripsin Inhibitor–BTCI protein. The stock samples herein studied are dextran coated maghemite nanoparticles (average core diameter of 7.1 nm, diameter dispersion of 0.26, and containing 4.6×1016 particle/mL) and the dextran coated maghemite nanoparticles associated with the BTCI protein. Several samples were prepared by diluting the stock samples with deionized water while following their colloidal stability. The diluted samples were investigated using SMB measurements to assess the average sizes of the self-assembled and suspended mesoscopic structures whereas the TEM micrographs provide the morphology of the as-suspended units. The SMB data were analyzed using a model that includes the particle-particle interaction within the mean field model picture.

Keywords: biocompatible magnetic fluid, maghemite nanoparticles, self-assembling

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Authors: W. P. Hu, J. V. Kumar, Jeffrey J. P. Tsai

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The inhibition of SH2 domain regulated protein-protein interactions is an attractive target for developing an effective chemotherapeutic approach in the treatment of disease. Molecular simulation is a useful tool for developing new drugs and for studying molecular recognition. In this study, we searched potential drug compounds for the inhibition of SH2 domain by performing structural similarity search in PubChem Compound Database. A total of 37 compounds were screened from the database, and then we used the LibDock docking program to evaluate the inhibition effect. The best three compounds (AP22408, CID 71463546 and CID 9917321) were chosen for MD simulations after the LibDock docking. Our results show that the compound CID 9917321 can produce a more stable protein-ligand complex compared to other two currently known inhibitors of Src SH2 domain. The compound CID 9917321 may be useful for the inhibition of SH2 domain based on these computational results. Subsequently experiments are needed to verify the effect of compound CID 9917321 on the SH2 domain in the future studies.

Keywords: nonpeptide inhibitor, Src SH2 domain, LibDock, molecular dynamics simulation

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Authors: Ryeong-Hyeon Kim, Ah-Reum Lee, Seong-Soo Roh, Gyo-Nam Kim

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Appropriate regulation of melanogenesis is important for the management of skin pigmentation-related disease. Although several beneficial effects of fisetin (3,7,3’,4’-tetrahydroxyflavone) have been reported, the precise role and molecular mechanisms of fisetin in skin health both remain unclear. Here, we induced melanogenesis of HRM2 mice (n=7/group) by UVB irradiation for 20 days. UVB-induced HRM2 mice showed that the significantly increased melanin accumulation, however, fisetin treatment (25mg and 50mg/kg of body weight) dose-dependently and significantly inhibits UVB-induced melanogenesis. In line with this, fisetin treatment effectively down-regulated m RNA and expression levels of tyrosinase, TRP2, and MITF. In addition, our inhibitor assay revealed the down-regulated melanogenic marker genes by fisetin treatment were mediated with connective tissue growth factor (CCN2)/TGF-β signaling pathway. Useful information is provided for development of functional foods using fisetin for skin health.

Keywords: connective tissue growth factor, fisetin, melanogenesis, skin, TGF-beta

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Authors: Rizwan H. Khan, Saima Nusrat

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Despite the fact that amyloid associated neurodegenerative diseases and non-neuropathic systemic amyloidosis have allured the research endeavors, as no curative drugs have been proclaimed up till now except for symptomatic cure. Therapeutic compounds which can diminish or disaggregate such toxic oligomers and fibrillar species have been examined and more are on its way. In the present study, we had reported an extensive biophysical, microscopic and computational study, revealing that L-3, 4-dihydroxyphenylalanine (L-Dopa) possess undeniable potency to inhibit heat induced human lysozyme (HL) amyloid fibrillation and also retain the fibril disaggregating potential. L-Dopa interferes in the amyloid fibrillogenesis process by interacting hydrophobically and also by forming hydrogen bonds with the amino acid residues found in amyloid fibril forming prone region of HL as elucidated by molecular docking results. L-Dopa also disaggregates the mature amyloid fibrils into some unorganised species. Thus, L-Dopa and related compounds can work as a promising inhibitor for the therapeutic advancement prospective against systemic amyloidosis.

Keywords: amyloids, disaggregation, human lysozyme, molecular docking

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Authors: Genaro Bolívar, Manuel Mas, Maria Tortolero, Jorge Salazar

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Due to the extensive use of water injection for oil displacement and pressure maintenance in oil fields, many reservoirs experience the problem of scale deposition when injection water starts to break through. In most cases the scaled-up wells are caused by the formation of sulfate and carbonate scales of calcium and strontium. Due to their relative hardness and low solubility, there are limited processes available for their removal and preventive measures such as the “squeeze” inhibitor treatment have to be taken. It is, therefore, important to gain a proper understanding of the kinetics of scale formation and its detrimental effects on formation damage under both inhibited and uninhibited conditions. Recently, the production of chitosan was started in our country and in the PDVSA-Intevep laboratories was synthesized and evaluated the properties of carboxymethyl chitosan (CMQ) as chelating agent of Ca2 + ions in water injection. In this regard, the characterization of the biopolymer by 13C - NMR, FTIR, TGA, and TM0374-2007 standard laboratory test has demonstrated the ability to remove up to 70% calcium ions in solution and shows a behavior that approaches that of commercial products.

Keywords: carboxymethyl chitosan, scale, calcium carbonate scale deposition, water injection

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Authors: Weijie Gu, Sergio Martinez, Hoai Nguyen, Hongtao Xu, Piet Herdewijn, Steven De Jonghe, Kalyan Das

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Nucleotide analogs are used for treating viral infections such as HIV, hepatitis B, hepatitis C, influenza, and SARS-CoV-2. To become polymerase substrates, a nucleotide analog must be phosphorylated by cellular kinases, which are rate-limiting. The goal of this study is to develop dNTP/NTP analogs directly from nucleotides. Tenofovir (TFV) analogs were synthesized by conjugating with natural or unnatural amino acids. It demonstrates that some conjugates act as dNTP analogs, and HIV-1 reverse transcriptase (RT) catalytically incorporates the TFV part as the chain terminator. X-ray structures in complex with HIV-1 RT/dsDNA showed binding of the conjugates at the polymerase active site, however, in different modes in the presence of Mg²⁺ vs. Mn²⁺ ions. The adaptability of the compounds is seemingly essential for catalytic incorporation of TFV by RT. 4d with a carboxyl sidechain demonstrated the highest incorporation. 4e showed weak incorporation and rather behaved as a dNTP-competitive inhibitor. This result advocates the feasibility of designing NTP/dNTP analogs by chemical substitutions to nucleotide analogs.

Keywords: dNTP analogs, nucleotide analogs, polymerase, tenofovir, X-ray structure

Procedia PDF Downloads 119

Authors: Rajesh P.P., Md. Tabish Noori, Makarand M. Ghangrekar

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Methanogenic substrate loss is reported to be a major bottleneck in microbial fuel cell which significantly reduces the power production capacity and coulombic efficiency (CE) of microbial fuel cell (MFC). Nitroethane is found to be a potent inhibitor of hydrogenotrophic methanogens in rumen fermentation process. Influence of nitroethane pre-treated sewage sludge inoculum on suppressing the methanogenic activity and enhancing the electrogenesis in MFC was evaluated. MFC inoculated with nitroethane pre-treated anodic inoculum demonstrated a maximum operating voltage of 541 mV, with coulombic efficiency and sustainable volumetric power density of 39.85 % and 14.63 W/m3 respectively. Linear sweep voltammetry indicated a higher electron discharge on the anode surface due to enhancement of electrogenic activity while suppressing methanogenic activity. A 63 % reduction in specific methanogenic activity was observed in anaerobic sludge pre-treated with nitroethane; emphasizing significance of this pretreatment for suppressing methanogenesis and its utility for enhancing electricity generation in MFC.

Keywords: coulombic efficiency, methanogenesis inhibition, microbial fuel cell, nitroethane

Procedia PDF Downloads 287

Authors: Kasim Sakran Abass

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This main aim of this study was to confirm and extend our current knowledge about the effects of dilutions on esterases activities in the blood for birds with respect to protecting the enzyme from organophosphate inhibition. There were significantly higher esterases activities in dilution 1:10 in all blood samples from quail, duck, and chick compared to other dilutions (1:5, 1:15, 1:20, and 1:25). Furthermore, our results also pointed to the importance of estimating different dilutions effects prior to using in birds as biomarker tools of environmental exposure. Concentration–inhibition curves were determined for the inhibitor in the presence of dilutions 1:5, 1:10 plus 1:15 (to stimulate carboxylesterase). Point estimates (concentrations calculated to produce 20, 50, and 80% inhibition) were compared across conditions and served as a measure of esterase-mediated detoxification. Among the thiol esters (dilution 1:5) was observed to have the highest specificity constant (kcat/Km), and the Km and kcat values were 176 μM and 16,765 s−1, respectively for S-phenyl thioacetate ester, while detected in (dilution 1:15) the lowest specificity constant (kcat/Km), and the Km and kcat values were 943 μM and 1154 s−1, respectively for acetylthiocholine iodide ester.

Keywords: esterase, animal, dilution, pesticides

Procedia PDF Downloads 497

Authors: K. N. Kipreou, E. Efthmiadou, G. Kordas

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Biofouling represents one of the most crucial problems in the present maritime industries when its control still challenges the researchers all over the world. The present work is referred to the synthesis and characterization CeMo and Cu2O nanocontainers by using a wide range of techniques including scanning electron microscopy (SEM), X-ray diffraction (XRD) and thermogravimetric analysis (TGA) for marine applications. The above nanosystems will be loaded with active monomers and corrosion rendering healing ability to marine paints. The objective of this project is their ability for self-healing, self-polishing and finally for anti-corrosion activity. One of the driving forces for the exploration of CeMo, is the unique anticorrosive behavior, which will be confirmed by the electrochemistry methodology. It has be highlighted that the nanocontainers of Cu2O with the appropriate antibacterial inhibitor will improve the hydrophobicity and the morphology of the coating surfaces reducing the water friction. In summary, both novel nanoc will increase the lifetime of the paints releasing the antifouling agent in a control manner.

Keywords: marinepaints, nanocontainer, antifouling, anticorrosion, copper, electrochemistry, coating, biofouling, inhibitors, copper oxide, coating, SEM

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Authors: Khalid Ahmed Eldwaib

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In this study, Al-Mg alloy 5052 was used as the testing material. Corrosion fatigue life was studied for the alloy in 3.5% NaCl (pH=1, 3, 5, 7, 9, and 11), and 3.5% NaCl (pH=1) with inhibitors. The compound inhibitors were composed mainly of phosphate (PO4³-), adding a certain proportion of other nontoxic inhibitors so as to select alternatives to environmentally hazardous chromate (Cr2O7²-). The inhibitors were sodium dichromate Na2Cr2O7, sodium phosphate Na3PO4, sodium molybdate Na2MoO4, and sodium citrate Na3C6H5O7. The total amount of inhibiting pigments was at different concentrations (250,500,750, and 1000 ppm) in the solutions. Corrosion fatigue behavior was studied by using plane-bending corrosion fatigue machine with stress ratio R=0.5 and under the constant frequency of 13.3 Hz. Results show that in 3.5% NaCl the highest fatigue life (number of cycles to failure Nf) is obtained at pH=5 where the oxide film on aluminum has very low solubility, and the lowest number of cycles is obtained at pH=1, where the media is too aggressive (extremely acidic). When the concentration of inhibitor increases the cycles to failure increase. The surface morphology and fracture section of the specimens had been characterized through scanning electron microscope (SEM).

Keywords: Al-Mg alloy 5052, corrosion, fatigue, inhibitors

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Authors: Venoos Iman, Suzita Mohd Noor, Syam Mohan, Mohamad Ibrahim Noordin

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Girinimbine, a carbazole alkaloid was isolated from the stem bark and root of Murraya koenigii and its structure and purity was identified by HPLC and LC-MS. Here we report that Girinimbine strongly inhibit angiogenesis activity both in vitro and in vivo. MTT result showed that girinimbine inhibits cell proliferation of the HUVECS cell line in vitro. Result of endothelial cell invasion, migration, tube formation and wound healing assays also demonstrated significant time and does dependent inhibition by girinimbine. Moreover, girinibine mediates its anti-angiogenic activity through up- and down-regulation of angiogenic and anti-aniogenic proteins. Furthermore, anti-angiogenic potential of girinimbine was evidenced in vivo on zebrafish model. Girinimbine inhibited neo-vessels formation in zebrafish embryos during 24 hours exposure time. Together, these results demonstrated for the first time that girinimbine could effectively suppress angiogenesis and strongly suggest that it might be a novel angiogenesis inhibitor.

Keywords: anti-angiogenic, carbazole alkaloid, girinimbine, zebrafish

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Authors: Olufunke O. Ezekiel, Adenike O. Ogunshe, Omotola F. Olagunju, Arinola O. Falola

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Studies were conducted on fermentation of tamarind seed for production of food condiment. Fermentation followed the conventional traditional method of fermented locust bean (iru) production and was carried out over a period of three days (72 hours). Samples were withdrawn and analysed for proximate composition, pH, titratable acidity, tannin content, phytic acid content and trypsin inhibitor activity using standard methods. Effects of fermentation on proximate composition, anti-nutritional factors and sensory properties of the seed were evaluated. All data were analysed using ANOVA and means separated using Duncan multiple range test. Microbiological analysis to identify and characterize the microflora responsible for the fermentation of the seed was also carried out. Fermentation had significant effect on the proximate composition on the fermented seeds. As fermentation progressed, there was significant reduction in the anti-nutrient contents. Organisms isolated from the fermenting tamarind seeds were identified as non-pathogenic and common with fermented legumes.

Keywords: condiment, fermentation, legume, tamarind seed

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Authors: Lyndsee Baumann-Birkbeck, Sohil A. Khan, Shailendra Anoopkumar-Dukie, Gary D. Grant

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Technology-enhanced education tools are being rapidly integrated into health programs globally. These tools provide an interactive platform for students and can be used to deliver topics in various modes including games and simulations. Simulations are of particular interest to healthcare education, where they are employed to enhance clinical knowledge and help to bridge the gap between theory and practice. Simulations will often assess competencies for practical tasks, yet limited research examines the effects of simulation on student perceptions of their learning. The aim of this study was to determine the effects of an interactive virtual patient simulation for pharmacology education and clinical practice on student knowledge, skills and confidence. Ethics approval for the study was obtained from Griffith University Research Ethics Committee (PHM/11/14/HREC). The simulation was intended to replicate the pharmacy environment and patient interaction. The content was designed to enhance knowledge of proton-pump inhibitor pharmacology, role in therapeutics and safe supply to patients. The tool was deployed into a third-year clinical pharmacology and therapeutics course. A number of core practice areas were examined including the competency domains of questioning, counselling, referral and product provision. Baseline measures of student self-reported knowledge, skills and confidence were taken prior to the simulation using a specifically designed questionnaire. A more extensive questionnaire was deployed following the virtual patient simulation, which also included measures of student engagement with the activity. A quiz assessing student factual and conceptual knowledge of proton-pump inhibitor pharmacology and related counselling information was also included in both questionnaires. Sixty-one students (response rate >95%) from two cohorts (2014 and 2015) participated in the study. Chi-square analyses were performed and data analysed using Fishers exact test. Results demonstrate that student knowledge, skills and confidence within the competency domains of questioning, counselling, referral and product provision, show improvement following the implementation of the virtual patient simulation. Statistically significant (p<0.05) improvement occurred in ten of the possible twelve self-reported measurement areas. Greatest magnitude of improvement occurred in the area of counselling (student confidence p<0.0001). Student confidence in all domains (questioning, counselling, referral and product provision) showed a marked increase. Student performance in the quiz also improved, demonstrating a 10% improvement overall for pharmacology knowledge and clinical practice following the simulation. Overall, 85% of students reported the simulation to be engaging and 93% of students felt the virtual patient simulation enhanced learning. The data suggests that the interactive virtual patient simulation developed for clinical pharmacology and therapeutics education enhanced students knowledge, skill and confidence, with respect to the competency domains of questioning, counselling, referral and product provision. These self-reported measures appear to translate to learning outcomes, as demonstrated by the improved student performance in the quiz assessment item. Future research of education using virtual simulation should seek to incorporate modern quantitative measures of student learning and engagement, such as eye tracking.

Keywords: clinical simulation, education, pharmacology, simulation, virtual learning

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Authors: Satya Srii, V., Nethra, N.

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An image analyzer system is described to study the process of imbibition in Melia dubia seeds. The experimental system consisted of control C (seeds with intact pericarp) with two treatments, namely T1 (seeds with pericarp punctured) and T2 (naked seeds without pericarp). The measurement software in the image analyzer can determine the area and perimeter as descriptors of changes in seed size during swelling resulting from imbibition. Using the area and perimeter parameter, the imbibition process in C, T1, and T2 was described by a series of curves similar to the triphasic pattern of water uptake, with the extent and rate depending upon the treatment. Naked seeds without pericarp (T2) took lesser time to reach phase III during imbition followed by seeds with pericarp punctured (T1) while the seeds with intact pericarp (C) were the slowest to attain phase III. This shows the effect of pericarp in acting as a potential inhibitor to imbibition inducing a large delay in germination. The sensitivity and feasibility of the method to investigate individual seeds within a population imply that the image analyzer has high potential in seed biology studies.

Keywords: germination, imbibition, image analyzer, Melia dubia, pericarp

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Authors: Doni Dermawan

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Hypertension is a disease with a high prevalence in Indonesia. The prevalence of hypertension in Indonesia is based on the Basic Health Research (Riskesdas) in 2013 which amounted to 25.8%. Medicinal plants have been widely used to treat hypertension including roselle (Hibiscus sabdariffa L.) and garlic (Allium sativum L.) by a mechanism as angiotensin converting enzyme (ACE) inhibitor. The purpose of this research is to analyze the in silico (molecular studies) of pharmacological effects and toxicity of roselle (Hibiscus sabdariffa L.) and garlic (Allium sativum L.) as well as a combination of both are used as antihypertensive herbs. The results of study showed that roselle (Hibiscus sabdariffa L.) and garlic (Allium sativum L.) have great potential as antihypertensive herbs based on the affinity and stability of active substances to specific receptor with a much better value than a of antihypertensive drugs (lisinopril). Toxicity values determined by the method of AST, ALT and ALP in which the three values obtained indicate the presence of acute toxic effects that need to be considered in determining the dose of the extract of roselle and garlic as antihypertensives.

Keywords: Allium sativum, antihypertensive, Hibiscus sabdariffa, in silico, toxicity

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Authors: Mosaab A. Omar, Mohammad Saleh Al-Aboody, Mohmed A. Rizk, Shimaa M. Elsayed, Ahmed ElSify, Naoaki Yokoyama, Ikuo Igarashi

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Enoxacin is a broad-spectrum 6-fluoronaphthyridinone antibacterial agent (fluoroquinolones) structurally related to nalidixic acid used mainly in the treatment of urinary tract infections and gonorrhea. Also, it has been shown recently that it may have cancer inhibiting effect. The primary antibabesial effect of Enoxacin is due to inhibition of DNA gyrase subunit A, and DNA topoisomerase. In the present study, enoxacin was tested as a potent inhibitor against the in vitro growth of bovine and equine Piroplasms. The in vitro growth of five Babesia species that were tested was significantly inhibited (P<0.05) by micromolar concentrations of enoxacin (IC50 values= 13.5, 7.2, 7.5, and 24.2 µM for Babesia bovis, Babesia bigemina, Babesia caballi, and Theileria equi, respectively). Enoxacin IC50 values for Babesia and Theileria parasites were satisfactory as the drug is a potent antibacterial drug with minimum side effects. Therefore, enoxacin might be used for the treatment of Babesiosis and Theileriosis especially in case of mixed infections with bacterial diseases or in the case of animal sensitivity against diminazin toxicity.

Keywords: enoxacin, Babesia, Theileria, IC50 and dimenazin

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Authors: Mohamed Deyab

Abstract:

The global lubricant additives market size was USD 14.35 billion in 2015. The industry is characterized by increasing additive usage in base oil blending for longer service life and performance. These additives improve the viscosity of oil, act as detergents, defoamers, antioxidants, and antiwear agents. Since additives play a significant role in base oil blending and subsequent formulations as they are critical materials in improving specification and performance of oils. Herein, we report on the synthesis and characterization of three imidazolium derivatives and their application as antioxidants, detergents and antiwear agents. The molecular structure and characterizations of these ionic liquids were confirmed by elemental analysis, FTIR, X-Ray Diffraction (XRD) and 1HNMR spectroscopy. Thermo gravimetric analysis (TGA), is used to study the degradation and thermal stability of the studied base stock samples. It was found that all the prepared ionic liquids additives have excellent power of dispersion and detergency. The ionic liquids as additives to engine oil reduced the friction (38%) and wear volume (76%) of steel balls. The obtained results show that the ionic liquids have an oxidation inhibitor up to 95%.

Keywords: reused lubricating oil, waste, petroleum, ionic liquids

Procedia PDF Downloads 106

Authors: Li Yuchen, Wu Qingxin, Jin Yuxing, Yang Qian

Abstract:

Interleukin-11 (IL-11), a well-known anti-inflammatory factor, helps to protect against intestinal epithelium damage caused by physical or chemical factors. However, little is known about the role of IL-11 during viral infection. Herein, high mRNA and protein levels of IL-11 were found in epithelial cells and jejunum of piglets during porcine epidemic diarrhea virus (PEDV) infection, and IL-11 expression was positively correlated with the level of viral infection. Pretreatment with recombinant porcine IL-11 (pIL-11) suppressed PEDV replication in Vero E6 cells, while IL-11 knockdown promoted viral infection. Furthermore, pIL-11 inhibited viral infection by preventing PEDV-mediated apoptosis of cells through activating the IL-11/STAT3 signal pathway. Conversely, application of a STAT3 phosphorylation inhibitor significantly antagonized the anti-apoptosis function of pIL-11 and counteracted its inhibition of PEDV. Our data suggested that that IL-11 is a novel PEDV-inducible cytokine, and its production enhances the anti-apoptosis ability of epithelial cells against PEDV infection. The potential uses of IL-11 as a novel therapeutic against devastating viral diarrhea in piglets deserves more attention and study.

Keywords: Interleukin-11, Porcine epidemic diarrhea virus, STAT3, anti-apoptosis

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Authors: Masoud Alipanah, Sekineh Akbari, Gholamreza Dashab

Abstract:

Myostatin genes or factor 8 affecting on growth and making differentiation works (GDF8) as a moderator in the development of skeletal muscle inhibitor. If mutations occurs in the coding region of myostatin, alter its inhibitory role and the muscle growth is increased. In this study, blood samples were collected randomly from 60 Kurdish sheep in northern Khorasan and DNA extraction was performed using a modified salt. A fragment 337 bp from exon 3 myostatin gene and-specific primers by using a polymerase chain reaction (PCR) were amplified. In order to detect different forms of an allele at this locus HaeΙΙΙ restriction enzymes and PCR-RFLP analysis were used. Band patterns clarification was performed using agarose gel electrophoresis. The frequency of genotypes mm, Mm, and MM, were respectively detected, 0, 0.15 and 0.85. The allele frequency for alleles m and M, were respectively, 0.07 and 0.93. The statistical analyses indicated that m allele was significantly associated with body weight. The results of this study suggest that the Myostatin gene possibly is a candidate gene that affects growth traits in Kurdish sheep.

Keywords: GDF8 gene, Kurdi Sheep of Northern Khorasan, polymorphism, weight traits

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Authors: Benarous Khedidja, Yousfi Mohamed

Abstract:

Infections caused by Candida species manifest in a number of diseases, including candidemia, vulvovaginal candidiasis, endocarditis, and peritonitis. These Candida species have been reported to have lipolytic activity by secretion of lipolytic enzymes such as esterases, lipases and phospholipases. These Extracellular hydrolytic enzymes seem to play an important role in Candida overgrowth. Candidiasis is commonly treated with antimycotics such as clotrimazole and nystatin, which bind to a major component of the fungal cell membrane (ergosterol). This binding forms pores in the membrane that lead to death of the fungus. Due to their secondary effects, scientists have thought of another treatment basing on lipase inhibition but we haven’t found any lipase inhibitors used as candidiasis treatment. In this work, we are interested to lipases inhibitors such as alkaloids as another candidiasis treatment. In the first part, we have proceeded to optimize the alkaloid structures and protein 3D structure using Hyperchem software. Secondly, we have docked inhibitors using Genetic algorithm with GOLD software. The results have shown ten possibilities of binding inhibitor to Candida rugosa lipase (CRL) but only one possibility has been accepted depending on the weakest binding energy.

Keywords: marrubiin, candida rugosa lipase, docking, gold

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Authors: Chung-Young Lee, Se-Hee Ahn, Jun-Gu Choi, Youn-Jeong Lee, Hyuk-Joon Kwon, Jae-Hong Kim

Abstract:

A/chicken/Korea/01310/2001 (H9N2) (01310) was passaged through embryonated chicken eggs (ECEs) by 20 times (01310-E20), and it has been used for an inactivated oil emulsion vaccine in Korea. After sequential passages, 01310-E20 showed higher pathogenicity in ECEs and acquired multiple mutations including a potential N-glycosylation at position 133 (H3 numbering) in HA and 18aa-deletion in NA stalk. To evaluate the effect of these mutations on the mammalian pathogenicity and resistance to non-specific inhibitors, we generated four PR8-derived recombinant viruses with different combinations of HA and NA from 01310-E2 and 01310-E20 (rH2N2, rH2N20, rH20N2, and rH20N20). According to our results, recombinant viruses containing 01310 E20 HA showed higher growth property in MDCK cells and higher virulence on mice than those containing 01310 E2 HA regardless of NA. The hemagglutination activity of rH20N20 was less inhibited by egg white and mouse lung extract than that of other recombinant viruses. Thus, the increased pathogenicity of 01310-E20 may be related to both higher replication efficiency and resistance to non-specific inhibitors in mice.

Keywords: avian influenza virus, egg adaptation, H9N2, N-glycosylation, stalk deletion of neuraminidase

Procedia PDF Downloads 259

Authors: N. A. Kazemi Sefat, M. M. Mohammadi, J. Hadjati, S. Talebi, M. Ajami, H. Daneshvar

Abstract:

Colorectal cancer metastases result in a significant number of cancer related deaths. Histone deacetylase (HDAC) inhibitors induce growth arrest and apoptosis in a variety of human cancer cells. Sodium butyrate (SB) is a short chain fatty acid, belongs to HDAC inhibitors which is released in the colonic lumen as a consequence of fiber fermentation. In this study, we are about to assess the effect of sodium butyrate on HCT116 human colorectal carcinoma cell line. The viability of cells was measured by microscopic morphologic study and MTT assay. After 48 hours, treatments more than 10 mM lead to cell injury in HCT116 by increasing cell granulation and decreasing cell adhesion (p>0.05). After 72 hours, treatments at 10 mM and more lead to significant cell injury (p<0.05). Our results may suggest that the gene expression which is contributed in cell proliferation and apoptosis has been changed under pressure of HDAC inhibition.

Keywords: colorectal cancer, sodium butyrate, cytotoxicity, MTT

Procedia PDF Downloads 332