Search results for: binding inhibitor

Authors: Muhasin Koyiloth, Sathyanarayana N. Gummadi

Abstract:

Biological membranes are ordered association of lipids, proteins, and carbohydrates. Lipids except sterols possess asymmetric distribution across the bilayer. Eukaryotic membranes possess a group of lipid translocators called scramblases that disrupt phospholipid asymmetry. Their action is implicated in cell activation during wound healing and phagocytic clearance of apoptotic cells. Cholesterol is one of the major membrane lipids distributed evenly on both the leaflet and can directly influence the membrane fluidity through the ordering effect. The fluidity has an impact on the activity of several membrane proteins. The palmitoylated phospholipid scramblases localized to the lipid raft which is characterized by a higher number of sterols. Here we propose that cholesterol can interact with scramblases through putative CRAC motif and can modulate their activity. To prove this, we reconstituted phospholipid scramblase 1 of C. elegans (SCRM-1) in proteoliposomes containing different amounts of cholesterol (Liquid ordered/Lo). We noted that the presence of cholesterol reduced the scramblase activity of wild-type SCRM-1. The interaction between SCRM-1 and cholesterol was confirmed by fluorescence spectroscopy using NBD-Chol. Also, we observed loss of such interaction when one of I273 in the CRAC motif mutated to Asp. Interestingly, the point mutant has partially retained scramblase activity in Lo vesicles. The current study elucidated the important interaction between cholesterol and SCRM-1 to fine-tune its activity in artificial membranes.

Keywords: artificial membranes, CRAC motif, plasma membrane, PL scramblase

Procedia PDF Downloads 169

Authors: Magdalena Rusady Goey, Gordon Strathdee, Neil Perkins

Abstract:

Background: Acute lymphoblastic leukaemia (ALL) is the most frequent type of childhood malignancy, accounting for 25% of all cases. TWIST2, a basic helix-loop-helix transcription factor, has been implicated in ALL development. Prior studies found that TWIST2 undergoes epigenetic silencing in more than 50% cases of ALL through promoter hypermethylation and suggested that re-expression of TWIST2 may inhibit cell growth/survival of leukaemia cell lines. TWIST2 has also been implicated as a regulator of NF-kappaB activity, which is constitutively active in leukaemia. Here, we use a lentiviral transductions system to confirm the importance of TWIST2 in controlling leukaemia cell growth and to investigate whether this is achieved through altered regulation of NF-kappaB activity. Method: Re-expression of TWIST2 in leukaemia cell lines was achieved using lentiviral-based transduction. The lentiviral vector also expresses enhanced green fluorescent protein (eGFP), allowing transduced cells to be tracked using flow cytometry. Analysis of apoptosis and cell proliferation were done using annexinV and VPD450 staining, respectively. Result and Discussion: TWIST2-expressing cells were rapidly depleted from a mixed population in ALL cell lines (NALM6 and Reh), indicating that TWIST2 inhibited cell growth/survival of ALL cells. In contrast, myeloid cell lines (HL60 and K562) were comparatively insensitive to TWIST2 re-expression. Analysis of apoptosis and cell proliferation found no significant induction of apoptosis, but did find a rapid induction of proliferation arrest in TWIST2-expressing Reh and NALM6 cells. Initial experiment with NF-kappaB inhibitor demonstrated that inhibition of NF-kappaB has similar impact on cell proliferation in the ALL cell lines, suggesting that TWITST2 may induce cell proliferation arrest through inhibition of NF-kappaB. Conclusion: The results of this study suggest that epigenetic inactivation of TWIST2 in primary ALL leads to increased proliferation, potentially by altering the regulation of NF-kappaB.

Keywords: leukaemia, acute lymphoblastic leukaemia, NF-kappaB, TWIST2, lentivirus

Procedia PDF Downloads 333

Authors: Schirin Hanf, Carlos Lizandara-Pueyo, Timmo P. Emmert, Ivana Jevtovikj, Roger Gläser, Stephan A. Schunk

Abstract:

Metal alkoxides are very versatile precursors for a broad array of complex functional materials. However, metal alkoxides, especially transition metal alkoxides, tend to form oligomeric structures due to the very strong M–O–M binding motif. This fact hinders their facile application in sol-gel-processes and complicates access to complex carbonate or oxidic compounds after hydrolysis of the precursors. Therefore, the development of a synthetic alternative with the aim to grant access to carbonates and hydroxycarbonates from simple metal alkoxide precursors via hydrolysis is key to this project. Our approach involves the reaction of metal alkoxides with unsaturated isoelectronic molecules, such as carbon dioxide. Subsequently, a stoichiometric insertion of the CO₂ into the alkoxide M–O bond takes place and leads to the formation of soluble metal alkyl carbonates. This strategy is a very elegant approach to solubilize metal alkoxide precursors to make them accessible for sol-gel chemistry. After hydrolysis of the metal alkyl carbonates, crystalline metal carbonates, and hydroxycarbonates can be obtained, which were then utilized for the synthesis of Cu/Zn based bulk catalysts for methanol synthesis. Using these catalysts, a comparable catalytic activity to commercially available MeOH catalysts could be reached. Based on these results, a complement for traditional precipitation techniques, which are usually utilized for the synthesis of bulk methanol catalysts, have been found based on an alternative solubilization strategy.

Keywords: metal alkoxides, metal carbonates, metal hydroxycarbonates, CO₂ insertion, solubilization

Procedia PDF Downloads 175

Authors: Harish Rajak, Preeti Patel

Abstract:

The application of histone deacetylase inhibitors is a well-known strategy in prevention of cancer which shows acceptable preclinical antitumor activity due to its ability of growth inhibition and apoptosis induction of cancer cell. Molecular docking were performed using Histone Deacetylase protein (PDB ID:1t69) and prepared series of hydroxamic acid based HDACIs. On the basis of docking study, it was predicted that compound 1 has significant binding interaction with HDAC protein and three hydrogen bond interactions takes place, which are essential for antitumor activity. On docking, most of the compounds exhibited better glide score values between -8 to -10 which is close to the glide score value of suberoylanilide hydroxamic acid. The pharmacophore hypotheses were developed using e-pharmacophore script and phase module. The 3D-QSAR models provided a good correlation between predicted and actual anticancer activity. Best QSAR model showed Q2 (0.7974), R2 (0.9200) and standard deviation (0.2308). QSAR visualization maps suggest that hydrogen bond acceptor groups at carbonyl group of cap region and hydrophobic groups at ortho, meta, para position of R9 were favorable for HDAC inhibitory activity. We established structure activity correlation using docking, pharmacophore modeling and atom based 3D QSAR model for hydroxamic acid based HDACIs.

Keywords: HDACIs, QSAR, e-pharmacophore, docking, suberoylanilide hydroxamic acid

Procedia PDF Downloads 291

Authors: Belete B. Beyene, Ayenew M. Mihirteu, Misganaw T. Ayana, Amogne W. Yibeltal

Abstract:

Modification of synthetic porphyrins is one of the promising strategies in an attempt to get molecules with desired properties and applications. Here in, we report synthesis, photophysical characterization and antibacterial activity of 5, 10, 15, 20-tetrakis-(4- methoxy carbonyl phenyl) porphyrin M(II); where M = Co, Fe, Ni, Zn. Metallation of the ligand was confirmed by using UV–Vis spectroscopy and ESI-Ms measurement, in which the number of Q bands in absorption spectra of the ligand decreased from four to one or two as a result of metal insertion to the porphyrin core. The antibacterial activity study of the complexes toward two Gram-positive (Staphylococcus aureus (S. aureus) and Streptococcus pyogenes (s. pyogenes)) and two Gram-negative (Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae)) bacteria by disc diffusion method showed a promising inhibitory activity. The complexes exhibited highest activities at highest concentration and were better than the activity of free base ligand, the salts, and blank solution. This could be explained on the basis of Overton's concept of cell permeability and Tweed's Chelation theory. An increased lipo-solubility enhances the penetration of the complexes into the lipid membrane and interferes with the normal activities of the bacteria. Our study, therefore, showed that the growth inhibitory effect of these metalloporphyrins is generally in order of ZnTPPCOOMe > NiTPPCOOMe > CoTPPCOOMe> FeTPPCOOMe, which may be attributed to the better lipophilicity and binding of the complex with the cellular components.

Keywords: porphyrins, metalloporphyrins, spectral property, antibacterial activity, synthesis

Procedia PDF Downloads 56

Authors: Rajapaksha Gedara Prasad Tharanga Jayasooriya, Matharage Gayani Dilshara, Yung Hyun Choi, Gi-Young Kim

Abstract:

Camptothecin (CPT) is a quinolone alkaloid which inhibits DNA topoisomerase I that induces cytotoxicity in a variety of cancer cell lines. We previously showed that CPT effectively inhibited invasion of prostate cancer cells and also combined treatment with subtoxic doses of CPT and TNF-related apoptosis-inducing ligand (TRAIL) potentially enhanced apoptosis in a caspase-dependent manner in hepatoma cancer cells. Here, we found that treatment with CPT caused an irreversible cell cycle arrest in the G2/M phase. CPT-induced cell cycle arrest was associated with a decrease in protein levels of cell division cycle 25C (Cdc25C) and increased the level of cyclin B and p21. The CPT-induced decrease in Cdc25C was blocked in the presence of proteasome inhibitor MG132, thus reversed the cell cycle arrest. In addition to that treatment of CPT-increased phosphorylation of Cdc25C was the resulted of activation of checkpoint kinase 2 (Chk2), which was associated with phosphorylation of ataxia telangiectasia-mutated. Interestingly CPT induced G2/M phase of the cell cycle arrest is reactive oxygen species (ROS) dependent where ROS inhibitors NAC and GSH reversed the CPT-induced cell cycle arrest. These results further confirm by using transient knockdown of nuclear factor-erythroid 2-related factor 2 (Nrf2) since it regulates the production of ROS. Our data reveal that treatment of siNrf2 increased the ROS level as well as further increased the CPT induce G2/M phase cell cycle arrest. Our data also indicate CPT-enhanced cell cycle arrest through the extracellular signal-regulated kinase (ERK) and the c-Jun N-terminal kinase (JNK) pathway. Inhibitors of ERK and JNK more decreased the Cdc25C expression and protein expression of p21 and cyclin B. These findings indicate that Chk2-mediated phosphorylation of Cdc25C plays a major role in G2/M arrest by CPT.

Keywords: camptothecin, cell cycle, checkpoint kinase 2, nuclear factor-erythroid 2-related factor 2, reactive oxygen species

Procedia PDF Downloads 423

Authors: Ilya B. Tsyrlov, Dmitry Y. Oshchepkov

Abstract:

A computational search for dioxin response elements (DREs) in genes of proteins comprising the Ah receptor (AhR) cytosolic core complex was performed by highly efficient tool SITECON. Eventually, the following number of new DREs in 5’flanking region was detected by SITECON: one in AHR gene, five in XAP2, eight in HSP90AA1, and three in HSP90AB1 genes. Numerous DREs found in genes of AhR and AhR cytosolic complex members would shed a light on potential mechanisms of expression, the stoichiometry of unliganded AhR core complex, and its degradation vs biosynthesis dynamics resulted from treatment of target cells with the AhR most potent ligand, 2,3,7,8-TCDD. With human viruses, reduced susceptibility to TCDD of geneencoding HIV-1 P247 was justified by the only potential DRE determined in gag gene encoding HIV-1 P24 protein, whereas the regulatory region of CMV genes encoding IE gp/UL37 has five potent DRE, 1.65 kb/UL36 – six DRE, pp65 and pp71 – each has seven DRE, and pp150 – ten DRE. Also, from six to eight DRE were determined with SITECON in the regulatory region of HSV-1 IE genes encoding tegument proteins, UL36 and UL37, and of UL19 gene encoding bindingglycoprotein C (gC). So, TCDD in the low picomolar range may activate in human cells AhR: Arnt transcription pathway that triggers CMV and HSV-1 reactivation by binding to numerous promoter DRE within immediate-early (IE) genes UL37 and UL36, thus committing virus to the lytic cycle.

Keywords: dioxin response elements, Ah receptor, AhR: Arnt transcription pathway, human and viral genes

Procedia PDF Downloads 97

Authors: Aliyu Maje Bello, Yaowaluck Maprang Roshorm

Abstract:

Hand, foot, and mouth disease (HFMD) is a highly contagious viral infection affecting mostly infants and children. Although the Enterovirus A71 (EV71) is usually the major causative agent of HFMD, other enteroviruses such as coxsackievirus A16, A10, and A6 are also found in some of the recent outbreaks. The commercially available vaccines have demonstrated their effectiveness against only EV71 infection but no protection against other enteroviruses. To address the limitation of the monovalent EV71 vaccine, the present study thus designed a tetravalent vaccine against the four major enteroviruses causing HFMD and primarily evaluated the designed vaccine using an immunoinformatics approach. The immunogen was designed to contain the EV71 VP1 protein and multiple reported epitopes from all four distinct enteroviruses and thus designated a tetravalent vaccine. The 3D structure of the designed tetravalent vaccine was modeled, refined, and validated. Epitope screening showed the presence of B-cell, CTL, CD4 T cell, and IFN epitopes with vast application among the Asian population. Docking analysis confirmed the stable and strong binding interactions between the immunogen and immune receptor B-cell receptor (BCR). In silico cloning and immune simulation analyses guaranteed high efficiency and sufficient expression of the vaccine candidate in humans. Overall, the promising results obtained from the in-silico studies of the proposed tetravalent vaccine make it a potential candidate worth further experimental validation.

Keywords: enteroviruses, coxsackieviruses, hand foot and mouth disease, immunoinformatics, tetravalent vaccine

Procedia PDF Downloads 56

Authors: Ayda Khosravanihaghighi, Pramod Koshy, Bill Walsh, Vedran Lovric, Charles Christopher Sorrell

Abstract:

There is an increasing demand for orthopedic implants owing to the increasing numbers of the aging population. Titanium alloy (Ti6Al4V) is a common material used for orthopedic implants owing to its advantageous properties in terms of good corrosion resistance, minimal elastic modulus mismatch with bone, bio-inertness, and high mechanical strength. However, it is important to improve the bioactivity and osseointegration of the titanium alloy and this can be achieved by coating the implant surface with suitable ceramic materials. In the present work, pure and doped-ceria (CeO₂) coatings were deposited by spin coating on the titanium alloy surface in order to enhance the biological interactions between the surface of the implant and the surrounding tissue. In order to examine the bone-binding ability of an implant, simulated body fluid (SBF) tests were conducted in order to assess the capability of apatite layer formation on the surface and thus predict in vivo bone bioactivity. Characterization was done using scanning electron microscopy (SEM) and X-ray diffraction (XRD) analyses to determine the extent of apatite formation. Preliminary tests showed that the CeO₂ coatings were biocompatible and that the extent of apatite formation and its characteristics can be enhanced by doping with suitable metal ions.

Keywords: apatite layer, biocompatibility, ceria, orthopaedic implant, SBF, spin coater, Ti-implant

Procedia PDF Downloads 143

Authors: Khaled M. Khleifat

Abstract:

Pseudomonas aeruginosa was isolated from infected burn patients and characterized by standard biochemical tests. The in vitro copper uptake was compared between this isolated pathogenic strain and two non-pathogenic control strains of Gram-positive bacteria Bacillusthuringiensis strain Israelisas well as Gram-negative bacteria Enterobacter aerogenes. Maximum copper uptake of 470 ppm/g biomass was obtained by P. aeruginosa strain, while the control strains B. thuringiensis and Enterobacter aerogenes had copper uptake of 350 and 383 ppm/g biomass, respectively. However, the lowest copper uptake (60 ppm/g biomass) was observed with another control the saprophytic strain Pseudomonas (Shewanella) putrefaciens. A further investigation regarding the effect of copper toxicity on bacterial growth, gave an MIC score of 600 ppm for P. aeruginosa strain compared to 460 and 300 ppm for the two Gram positive and Gram negative control strains, respectively. In tandem with these in vitro findings, blood analysis on burn patients infected with P. aeruginosa has indicated a selective decrease of copper (hypocupremia) and ceruloplasmin plasma levels. The iron metabolism was also affected by this copper deprivation leading to a similar decrease in plasma levels of PCV, iron, total iron-binding capacity, and transferrin. All these hematological changes were significantly different (P < 0.05) from the matched group of non-infected burn patients. The observed hypocupremia in infected burn patients was attributed to demanding scavenger ability by P. aeruginosa strain for the copper of plasma.

Keywords: Pseudomonas aeruginosa, hypocupremia, correlation, PCV

Procedia PDF Downloads 300

Authors: Arunava Chakrabarti

Abstract:

A one-dimensional chain of magnetic atoms, representative of a quantum gas in an artificial quasi-periodic potential and modeled by the well-known Aubry-Andre function and its variants are studied in respect of its capability of working as a spin filter for arbitrary spins. The basic formulation is explained in terms of a perfectly periodic chain first, where it is shown that a definite correlation between the spin S of the incoming particles and the magnetic moment h of the substrate atoms can open up a gap in the energy spectrum. This is crucial for a spin filtering action. The simple one-dimensional chain is shown to be equivalent to a 2S+1 strand ladder network. This equivalence is exploited to work out the condition for the opening of gaps. The formulation is then applied for a one-dimensional chain with quasi-periodic variation in the site potentials, the magnetic moments and their orientations following an Aubry-Andre modulation and its variants. In addition, we show that a certain correlation between the system parameters can generate absolutely continuous bands in such systems populated by Bloch like extended wave functions only, signaling the possibility of a metal-insulator transition. This is a case of correlated disorder (a deterministic one), and the results provide a non-trivial variation to the famous Anderson localization problem. We have worked within a tight binding formalism and have presented explicit results for the spin half, spin one, three halves and spin five half particles incident on the magnetic chain to explain our scheme and the central results.

Keywords: Aubry-Andre model, correlated disorder, localization, spin filter

Procedia PDF Downloads 347

Authors: Majid Farsadrooh, Mehran Feizi-Dehnayebi

Abstract:

Serum albumin is the most abundant protein that is present in the circulatory system of a wide variety of organisms. Although it is a significant macromolecule, it can contribute to osmotic blood pressure and also, plays a superior role in drug disposition and efficiency. Molecular docking simulation can improve in silico drug design and discovery procedures to propound a lead compound and develop it from the discovery step to the clinic. In this study, the molecular docking simulation was applied to select a lead molecule through an investigation of the interaction of the two anticancer drugs (Alitretinoin and Abemaciclib) with Human Serum Albumin (HSA). Then, a series of new compounds (a-e) were suggested using lead molecule modification. Density functional theory (DFT) including MEP map and HOMO-LUMO analysis were used for the newly proposed compounds to predict the reactivity zones on the molecules, stability, and chemical reactivity. DFT calculation illustrated that these new compounds were stable. The estimated binding free energy (ΔG) values for a-e compounds were obtained as -5.78, -5.81, -5.95, -5,98, and -6.11 kcal/mol, respectively. Finally, the pharmaceutical properties and toxicity of these new compounds were estimated through OSIRIS DataWarrior software. The results indicated no risk of tumorigenic, irritant, or reproductive effects and mutagenicity for compounds d and e. As a result, compounds d and e, could be selected for further study as potential therapeutic candidates. Moreover, employing molecular docking simulation with the prediction of pharmaceutical properties helps to discover new potential drug compounds.

Keywords: drug design, anticancer, computational studies, DFT analysis

Procedia PDF Downloads 63

Authors: Lu Yang, Keng Po Lai

Abstract:

Metformin, a well-known clinical drug against diabetes, is found with potential anti-diabetic and anti-obese benefits, as reported in increasing evidences. However, the current clinical and experimental investigations are not to reveal the detailed mechanisms of metformin-anti-obesity/hypertension. We have used the bioinformatics strategy, including network pharmacology and molecular docking methodology, to uncover the key targets and pathways of bioactive compounds against clinical disorders, such as cancers, coronavirus disease. Thus, in this report, the in-silico approach was utilized to identify the hug targets, pharmacological function, and mechanism of metformin against obesity and hypertension. The networking analysis identified 154 differentially expressed genes of obesity and hypertension, 21 interaction genes, and 6 hug genes of metformin treating hypertensive obesity. As a result, the molecular docking findings indicated the potent binding capability of metformin with the key proteins, including interleukin 6 (IL-6) and chemokine (C-C motif) Ligand 2 (CCL2), in hypertensive obesity. The metformin-exerted anti-hypertensive obesity action involved in metabolic regulation, inflammatory reaction. And the anti-hypertensive obesity mechanisms of metformin were revealed, including regulation of inflammatory and immunological signaling pathways for metabolic homeostasis in tissue and microenvironmental melioration in blood pressure. In conclusion, our identified findings with bioinformatics analysis have demonstrated the detailed hug and pharmacological targets, biological functions, and signaling pathways of metformin treating hypertensive obesity.

Keywords: metformin, obesity, hypertension, bioinformatics findings

Procedia PDF Downloads 111

Authors: Shilpa Khobragade, Carlos Da Silva Granja, Niklas Sandström, Igor Efimov, Victor P. Ostanin, Wouter van der Wijngaart, David Klenerman, Sourav K. Ghosh

Abstract:

Rapid, label-free and direct detection of pathogenic bacteria is critical for the prevention of disease outbreaks. This paper for the first time attempts to probe the nonlinear acoustic response of quartz crystal resonator (QCR) functionalized with specific DNA aptamers for direct detection and quantification of viable E. coli KCTC 2571 bacteria. DNA aptamers were immobilized through biotin and streptavidin conjugation, onto the gold surface of QCR to capture the target bacteria and the detection was accomplished by shift in amplitude of the peak 3f signal (3 times the drive frequency) upon binding, when driven near fundamental resonance frequency. The developed nonlinear acoustic aptasensor system demonstrated better reliability than conventional resonance frequency shift and energy dissipation monitoring that were recorded simultaneously. This sensing system could directly detect 10⁽⁵⁾ cells/mL target bacteria within 30 min or less and had high specificity towards E. coli KCTC 2571 bacteria as compared to the same concentration of S.typhi bacteria. Aptasensor response was observed for the bacterial suspensions ranging from 10⁽⁵⁾-10⁽⁸⁾ cells/mL. Conclusively, this nonlinear acoustic aptasensor is simple to use, gives real-time output, cost-effective and has the potential for rapid, specific, label-free direction detection of bacteria.

Keywords: acoustic, aptasensor, detection, nonlinear

Procedia PDF Downloads 552

Authors: Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan

Abstract:

Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have comprehensively evaluated Mre11 in epithelial ovarian cancers. In clinical cohort that received platinum- based chemotherapy (n=331), Mre11 protein overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p=0.002). In the ovarian cancer genome atlas (TCGA) cohort (n=498), Mre11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with Mre11 mRNA levels (p<0.0001). Altered Mre11 levels was linked with genome wide alterations that can influence platinum sensitivity. At the transcriptomic level (n=1259), Mre11 overexpression was associated with poor PFS (p=0.003). ROC analysis showed an area under the curve (AUC) of 0.642 for response to platinum-based chemotherapy. Pre-clinically, Mre11 depletion by gene knock down or blockade by small molecule inhibitor (Mirin) reversed platinum resistance in ovarian cancer cells and in 3D spheroid models. Importantly, Mre11 inhibition was synthetically lethal in platinum sensitive XRCC1 deficient ovarian cancer cells and 3D-spheroids. Selective cytotoxicity was associated with DNA double strand break (DSB) accumulation, S-phase cell cycle arrest and increased apoptosis. We conclude that pharmaceutical development of Mre11 inhibitors is a viable clinical strategy for platinum sensitization and synthetic lethality in ovarian cancer.

Keywords: MRE11; XRCC1, ovarian cancer, platinum sensitization, synthetic lethality

Procedia PDF Downloads 116

Authors: Yasmin Begum Mohammed

Abstract:

Ketorolac tromethamine (KTM) is a non-steroidal anti-inflammatory drug with a potent analgesic and anti-inflammatory activity due to prostaglandin related inhibitory effect of drug. It is a non-selective cyclo-oxygenase inhibitor. The drug is currently used orally and intramuscularly in multiple divided doses, clinically for the management arthritis, cancer pain, post-surgical pain, and in the treatment of migraine pain. KTM has short biological half-life of 4 to 6 hours, which necessitates frequent dosing to retain the action. The frequent occurrence of gastrointestinal bleeding, perforation, peptic ulceration, and renal failure lead to the development of other drug delivery strategies for the appropriate delivery of KTM. The ideal solution would be to target the drug only to the cells or tissues affected by the disease. Drug targeting could be achieved effectively by liposomes that are biocompatible and biodegradable. The aim of the study was to develop a parenteral liposome formulation of KTM with improved efficacy while reducing side effects by targeting the inflammation due to arthritis. PEG-anchored (stealth) and non-PEG-anchored liposomes were prepared by thin film hydration technique followed by extrusion cycle and characterized for in vitro and in vivo. Stealth liposomes (SLs) exhibited increase in percent encapsulation efficiency (94%) and 52% percent of drug retention during release studies in 24 h with good stability for a period of 1 month at -20°C and 4°C. SLs showed about maximum 55% of edema inhibition with significant analgesic effect. SLs produced marked differences over those of non-SL formulations with an increase in area under plasma concentration time curve, t₁/₂, mean residence time, and reduced clearance. 0.3% of the drug was detected in arthritic induced paw with significantly reduced drug localization in liver, spleen, and kidney for SLs when compared to other conventional liposomes. Thus SLs help to increase the therapeutic efficacy of KTM by increasing the targeting potential at the inflammatory region.

Keywords: biodistribution, ketorolac tromethamine, stealth liposomes, thin film hydration technique

Procedia PDF Downloads 282

Authors: Samuel Abebe Ebebo

Abstract:

Scale precipitation causes a major issue for geothermal power plants because it reduces the production rate of geothermal energy. Each geothermal power plant's different chemical and physical conditions can cause the scale to precipitate under a particular set of fluid-rock interactions. Depending on the mineral, it is possible to have scale in the production well, steam separators, heat exchangers, reinjection wells, and everywhere in between. The scale consists mainly of smectite and trace amounts of chlorite, magnetite, quartz, hematite, dolomite, aragonite, and amorphous silica. The smectite scale is one of the difficult scales at injection wells in geothermal power plants. X-ray diffraction and chemical composition identify this smectite as Stevensite. The characteristics and the scale of each injection well line are different depending on the fluid chemistry. The smectite scale has been widely distributed in pipelines and surface plants. Mineral water equilibrium showed that the main factors controlling the saturation indices of smectite increased pH and dissolved Mg concentration due to the precipitate on the equipment surface. This study aims to characterize the scales and geothermal fluids collected from the Onuma geothermal power plant in Akita Prefecture, Japan. Field tests were conducted on October 30–November 3, 2021, at Onuma to determine the pH control methods for preventing magnesium silicate scaling, and as exemplified, the formation of magnesium silicate hydrates (M-S-H) with MgO to SiO2 ratios of 1.0 and pH values of 10 for one day has been studied at 25 °C. As a result, M-S-H scale formation could be suppressed, and stevensite formation could also be suppressed when we can decrease the pH of the fluid by less than 8.1, 7.4, and 8 (at 97 °C) in the fluid from O-3Rb and O-6Rb, O-10Rg, and O-12R, respectively. In this context, the scales and fluids collected from injection wells at a geothermal power plant in Japan were analyzed and characterized to understand the formation conditions of Mg-silicate scales with on-site synthesis experiments. From the results of the characterizations and on-site synthesis experiments, the inhibition method of their scale formation is discussed based on geochemical modeling in this study.

Keywords: magnesium silicate, scaling, inhibitor, geothermal power plant

Procedia PDF Downloads 50

Authors: Maxime Moreau, Silvère Baron, Jean-Marc Lobaccaro, Karine Charlet, Sébastien Menecier, Frédéric Perisse

Abstract:

Cold Atmospheric Plasma (CAP) is an ionized gas generated at atmospheric pressure with the temperature of heavy particles (molecules, ions, atoms) close to the room temperature. Recent studies have shown that both in-vitro and in-vivo plasma exposition to many cancer cell lines are efficient to induce the apoptotic way of cell death. In some other works, normal cell lines seem to be less impacted by plasma than cancer cell lines. This is called selectivity of plasma. It is highly likely that the generated RNOS (Reactive Nitrogen Oxygen Species) in the plasma jet, but also in the medium, play a key-role in this selectivity. In this study, two CAP devices will be compared to electrical power, chemical species composition and their efficiency to kill cancer cells. A particular focus on the action of hydrogen peroxide will be made. The experiments will take place as described next for both devices: electrical and spectroscopic characterization for different voltages, plasma treatment of normal and cancer cells to compare the CAP efficiency between cell lines and to show that death is induced by an oxidative stress. To enlighten the importance of hydrogen peroxide, an inhibitor of H2O2 will be added in cell culture medium before treatment and a comparison will be made between the results of cell viability in this case and those from a simple plasma exposition. Besides, H2O2 production will be measured by only treating medium with plasma. Cell lines will also be exposed to different concentrations of hydrogen peroxide in order to characterize the cytotoxic threshold for cells and to make a comparison with the quantity of H2O2 produced by CAP devices. Finally, the activity of catalase for different cell lines will be quantified. This enzyme is an important antioxidant agent against hydrogen peroxide. A correlation between cells response to plasma exposition and this activity could be a strong argument in favor of the predominant role of H2O2 to explain the selectivity of plasma cancer treatment by cold atmospheric plasma.

Keywords: cold atmospheric plasma, hydrogen peroxide, prostate cancer, selectivity

Procedia PDF Downloads 136

Authors: Zerrin Orbak, Busra Demir

Abstract:

Osteopetrosis is a rare genetic disease characterized by impaired bone resorption and increased bone sclerosis. Clinical presentation is very different in osteopetrosis. It can be asymptomatic or can be seen with typical symptoms. Here, a case of osteopetrosis was presented when evaluated for nystagmus. She was 10 months old. Parents were second-degree relatives. On physical examination, pigeon chest deformity and horizontal nystagmus were observed. There was a failure of thrive but no fracture. The cardiovascular examination was normal. Cranial, vertebral and long bone roentgenograms revealed characteristic deformities of osteopetrosis and diffuse sclerosis. The diagnosis was confirmed by genetic testing. A Homozygous mutation was detected in the TNFRSF11A gene (c.508A>G p.(Arg170Gly)). RANKL is encoded by the tumor necrosis factor ligand superfamily member 11 (TNFSF11) gene, and the binding to its receptor RANK, encoded by the TNFRSF11A gene, determines the activation of the downstream pathway that drives osteoclast differentiation and activation (51). The complete absence of osteoclasts is the key feature of the osteoclast-poor form of osteopetrosis (46). Patients are characterized by the absence of TRAP-positive osteoclasts in bone biopsies. The osteoclast-poor subtype of osteopetrosis caused by mutations in TNFSF11 gene is ultra-rare in humans. Clinical presentation is usually severe, with onset in early infancy or in fetal life. But here, a case was presented with horizontal nystagmus. A case presented with horizontal nystagmus, which was evaluated by neurology and diagnosed incidentally, was shared.

Keywords: osteopetrosis, nystagmus, bone, osteoclast-poor

Procedia PDF Downloads 76

Authors: James Patrick A. Diaz, Raul E. Ramboyong

Abstract:

Background: Hypertensive response during maximal exercise test provides important information on the level of blood pressure control and evaluation of treatment. Method: A single center retrospective descriptive study was conducted among 117 young (aged 20 to 40) and middle age (aged 40 to 65) hypertensive patients, who underwent treadmill stress test. Currently on maintenance frontline medication either monotherapy (Angiotensin-converting enzyme inhibitor/Angiotensin receptor blocker [ACEi/ARB], Calcium channel blocker [CCB], Diuretic - Hydrochlorthiazide [HCTZ]) or combination therapy (ARB+CCB, ARB+HCTZ), who attained a maximal exercise on treadmill stress test (TMST) with hypertensive response (systolic blood pressure: male >210 mm Hg, female >190 mm Hg, diastolic blood pressure >100 mmHg, or increase of >10 mm Hg at any time during the test), on Bruce and Modified Bruce protocol. Exaggerated blood pressure response during exercise (systolic [SBP] and diastolic [DBP]), peak exercise blood pressure (SBP and DBP), recovery period (SBP and DBP) and test for ischemia and their antihypertensive medication/s were investigated. Analysis of variance and chi-square test were used for statistical analysis. Results: Hypertensive responses on maximal exercise test were seen mostly among female population (P < 0.000) and middle age (P < 0.000) patients. Exaggerated diastolic blood pressure responses were significantly lower in patients who were taking CCB (P < 0.004). A longer recovery period that showed a delayed decline in SBP was observed in patients taking ARB+HCTZ (P < 0.036). There were no significant differences in the level of exaggerated systolic blood pressure response and during peak exercise (both systolic and diastolic) in patients using either monotherapy or combination antihypertensives. Conclusion: Calcium channel blockers provided lower exaggerated diastolic BP response during maximal exercise test in hypertensive middle age patients. Patients on combination therapy using ARB+HCTZ exhibited a longer recovery period of systolic blood pressure.

Keywords: antihypertensive, exercise test, hypertension, hyperytensive response

Procedia PDF Downloads 272

Authors: Hao Cheng, Yingzhou Ni, Amr M. Bakry, Li Liang

Abstract:

Functional foods containing bioactive nutrients offer benefits beyond basic nutrition and hence the possibility of delaying and preventing chronic diseases. However, many bioactive nutrients degrade rapidly under food processing and storage conditions. Encapsulation can be used to overcome these limitations. Food proteins have been widely used as carrier materials for the preparation of nano/micro-particles because of their ability to form gels and emulsions and to interact with polysaccharides. The mechanisms of interaction between bioactive nutrients and proteins must be understood in order to develop protein-based lipid-free delivery systems. Beta-lactoglobulin, a small globular protein in milk whey, exhibits an affinity to a wide range of compounds. Alfa-tocopherol, resveratrol and folic acid were respectively bound to the central cavity, the outer surface near Trp19–Arg124 and the hydrophobic pocket in the groove between the alfa-helix and the beta-barrel of the protein. Beta-lactoglobulin could thus bind the three bioactive nutrients simultaneously to form protein-multi-ligand complexes. Beta-casein, an intrinsically unstructured but major milk protein, could also interact with resveratrol and folic acid to form complexes. These results suggest the potential to develop milk-protein-based complex carrier systems for encapsulation of multiple bioactive nutrients for functional food application and also pharmaceutical and medical uses.

Keywords: milk protein, bioactive nutrient, interaction, protection

Procedia PDF Downloads 401

Authors: Don Buddika Oshadi Malaweera, Lora Harris, Bruce Rathgeber, Chibuike C. Udenigwe, Kirsti Rouvinen-Watt

Abstract:

Fatty liver disease is among the three most severe health concerns for mink and believed to occur through the same mechanism as nursing sickness. In North America, nursing sickness affects about 45% of mink farms and in Canada, approximately 50,000 mink females is affected annually. Orotic acid (OA) plays a critical role in lipid metabolism and can increase hepatic lipids by enhancing Sterol regulatory element binding protein-1c expression and decreasing Carnitine palmitoyl transferase I activity. This study was conducted to identify particular pathways and regulatory control points involved in fatty liver development, and evaluate the effectiveness of arginine and bioactive peptides for prevention and treatment of fatty liver disease in mink. A total of 45 mink were used in 9 treatments. The experimental diets consisted of 1% OA, 2% L-arginine and 5% of whey protein hydrolysates. At the end of 10 days of experimental period, the mink were anaesthetized, sampled for blood and euthanized, samples were obtained for histological, biochemical and molecular assays. The blood samples will be analyzed for clinical chemistry and triacylglycerol. The liver samples will be analyzed for total lipid content and analyzed for 6 genes of interest involved in adipogenic transformation, ER stress, and liver inflammation.

Keywords: fatty liver, L-arginine, mink, orotic acid, whey protein hydrolysates

Procedia PDF Downloads 293

Authors: Lynn Louis, Bor Shin Chee, Marion McAfee, Michael Nugent

Abstract:

This article aims to develop a sustained release formulation of microspheres containing the mTOR inhibitor Everolimus (EVR) using Polyvinyl alcohol (PVA) to enhance the bioavailability of the drug and to overcome poor solubility characteristics of Everolimus. This paper builds on recent work in the manufacture of microspheres using the sessile droplet technique by freezing the polymer-drug solution by suspending the droplets into pre-cooled ethanol vials immersed in liquid nitrogen. The spheres were subjected to 6 freezing cycles and 3 freezing cycles with thawing to obtain proper geometry, prevent aggregation, and achieve physical cross-linking. The prepared microspheres were characterised for surface morphology by SEM, where a 3-D porous structure was observed. The in vitro release studies showed a 62.17% release over 12.5 days, indicating a sustained release due to good encapsulation. This result is comparatively much more than the 49.06% release achieved within 4 hours from the solvent cast Everolimus film as a control with no freeze-thaw cycles performed. The solvent cast films were made in this work for comparison. A prolonged release of Everolimus using a polymer-based drug delivery system is essential to reach optimal therapeutic concentrations in treating SEGA tumours without systemic exposure. These results suggest that the combination of PVA and Everolimus via a rheological synergism enhanced the bioavailability of the hydrophobic drug Everolimus. Physical-chemical characterisation using DSC and FTIR analysis showed compatibility of the drug with the polymer, and the stability of the drug was maintained owing to the high molecular weight of the PVA. The obtained results indicate that the developed PVA/EVR microsphere is highly suitable as a potential drug delivery system with improved bioavailability in treating Subependymal Giant cell astrocytoma (SEGA).

Keywords: drug delivery system, everolimus, freeze-thaw cycles, polyvinyl alcohol

Procedia PDF Downloads 108

Authors: Vighnesh Daas, David B. Tann, Mahmood Datoo

Abstract:

The incorporation of recycled plastic fibres in concrete as reinforcement is a potential sustainable alternative for replacement of ordinary steel bars. It provides a scope for waste reduction and re-use of plastics in the construction industry on a large scale. Structural use of fibre reinforced concrete is limited to short span members and low reliability classes. In this study, recycled carpet fibres made of 95% polypropylene with length of 45mm were used for experimental investigations. The performance of recycled polypropylene fibres under structural loading has been compared with commercially available virgin fibres at low volume fractions of less than 1%. A series of 100 mm cubes and 125x200x2000 mm beams were used to conduct strength tests in bending and compression to measure the influence of type and volume of fibres on the structural behaviour of fibre reinforced concrete beams. The workability of the concrete mix decreased as a function of fibre content and resulted in a modification of the mix design. The beams failed in a pseudo-ductile manner with an enhanced bending capacity. The specimens showed significant improvement in the post-cracking behaviour and load carrying ability as compared to conventional reinforced concrete members. This was associated to the binding properties of the fibres in the concrete matrix. With the inclusion of fibres at low volumes of 0-0.5%, there was reduction in crack sizes and deflection. This study indicates that the inclusion of recycled polypropylene fibres at low volumes augments the structural behaviour of concrete as compared to conventional reinforced concrete as well as virgin fibre reinforced concrete.

Keywords: fibre reinforced concrete, polypropylene, recycled, strength

Procedia PDF Downloads 233

Authors: Małgorzata Osowiecka

Abstract:

Negative emotions are rather seen as creativity inhibitor. On the other hand, it is worth noting that negative emotions may be good for our functioning. Negative emotions enhance cognitive resources and improve evaluative processes. Moreover maintaining a negative emotional state allow for cognitive reinterpretation of the emotional stimuli, what is good for our creativity, especially cognitive flexibility. Writing a diary or writing about difficult emotional experiences in general can be the way to not only improve psychical health, but also – enhance creative behaviors. Thanks to translating difficult emotions to the verbal level and giving them ‘a name’ or ‘a label’, we can get easier access to both emotional content of an experience and to the semantic content, without the need of speaking out loud. Expressive writing improves academic results and the efficiency of working memory. The classical method of writing about emotions consists in a long-term process of describing negative experiences. Present research demonstrate the efficiency of this process over a shorter period of time - one writing session, on school children sample. Participants performed writing task. Writing task had two different topics: emotions connected with their negative emotions (expressive writing) and content not connected with negative emotional state (writing about one’s typical day). Creativity was measured by Guilford’s Alternative Uses Task. Results have shown that writing about negative emotions results in the higher level of divergent thinking in all three parameters: fluency, flexibility and originality. After the writing task mood of expressive writing participants remained negative more than the mood of the controls. Taking an expressive action after a difficult emotional experience can support functioning, which can be observed in enhancement of divergent thinking. Writing about emotions connected with negative experience makes one more creative, than writing about something unrelated with difficult emotional moments. Research has shown that young people should not demonize negative emotions. Sometimes, properly applied, negative emotions can be the basis of creation. Preparation was supported by a The Young Scientist University grant titled ‘Dynamics of emotions in the creative process’ from The Polish Ministry of Science and Higher Education.

Keywords: creativity, divergent thinking, emotions, expressive writing

Procedia PDF Downloads 179

Authors: Deepika Saini, Sandeep Jain, Ajay Kumar

Abstract:

The quinoline scaffold is one of the most widely studied in the discovery of derivatives with various heterocyclic moieties due to its potential antimalarial activities. In the present study, a chalcone series of quinoline derivatives clubbed with pyrazole were synthesized to evaluate their antimalarial property by in vitro schizont maturation inhibition assay against both chloroquine sensitive, 3D7 and chloroquine resistant, RKL9 strain of Plasmodium falciparum. Further, top five compounds were studied for in vivo preclinical study for antimalarial potential against P. berghei in Swiss albino mice. To understand the mechanism of synthesized analogues, they were screened computationally by molecular docking techniques. Compounds were docked into the active site of a protein receptor, Plasmodium falciparum Cysteine Protease Falcipain-2. The compounds were successfully synthesized, and structural confirmation was performed by FTIR, 1H-NMR, mass spectrometry and elemental analysis. In vitro study suggested that the compounds 5b, 5g, 5l, 5s and 5u possessed best antimalarial activity and further tested for in vivo screening. Compound 5u (CH₃ on both rings) with EC₅₀ 0.313 & 0.801 µg/ml against CQ-S & CQ-R strains of P. falciparum respectively and 78.01% suppression of parasitemia. The molecular docking studies of the compounds helped in understanding the mechanism of action against falcipain-2. The present study reveals the binding signatures of the synthesized ligands within the active site of the protein, and it explains the results from in vitro study in their EC₅₀ values and percentage parasitemia.

Keywords: antimalarial activity, chalcone, docking, quinoline

Procedia PDF Downloads 396

Authors: Amit Kumar, Davide Lionetti, Victor Day, James Blakemore

Abstract:

Capture and activation of the water-soluble uranyl dication (UO22+) remains a challenging problem, as few rational approaches are available for modulating the reactivity of this species. Here, we report the divergent synthesis of heterobimetallic complexes in which UO22+ is held in close proximity to a range of redox-inactive metals by tailored macrocyclic ligands. Crystallographic and spectroscopic studies confirm assembly of homologous UVI(μ-OAr)2Mn+ cores with a range of mono-, di-, and trivalent Lewis acids (Mn+). X-ray diffraction (XRD) and cyclic voltammetry (CV) data suggest preferential binding of K+ in an 18-crown-6-like cavity and Na+ in a 15-crown-5-like cavity, both appended to Schiff-base type sites that selectively bind UO22+. CV data demonstrate that the UVI/UV reduction potential in these complexes shifts positive and the rate of electron transfer decreases with increasing Lewis acidity of the incorporated redox-inactive metals. Moreover, spectroelectrochemical studies confirm the formation of [UV] species in the case of monometallic UO22+ complex, consistent with results from prior studies. However, unique features were observed during spectroelectrochemical studies in the presence of the K+ ion, suggesting new insights into electronic structure may be accessible with the heterobimetallic complexes. Overall, these findings suggest that interactions with Lewis acids could be effectively leveraged for rational tuning of the electronic and thermochemical properties of the 5f elements, reminiscent of strategies more commonly employed with 3d transition metals.

Keywords: electrochemistry, Lewis acid, macrocycle, uranyl

Procedia PDF Downloads 130

Authors: Padmalochan Panda, R. Ramaseshan

Abstract:

Aluminum nitride (AlN) is a potential candidate for semiconductor industry due to its wide band gap (6.2 eV), high thermal conductivity and low thermal coefficient of expansion. A-plane oriented AlN film finds an important role in deep UV-LED with higher isotropic light extraction efficiency. Also, Cr-doped AlN films exhibit dilute magnetic semiconductor property with high Curie temperature (300 K), and thus compatible with modern day microelectronics. In this work, highly a-axis oriented wurtzite AlN and Al1-xMxN (M = Cr, Ti) films have synthesized by reactive co-sputtering technique at different concentration. Crystal structure of these films is studied by Grazing incidence X-ray diffraction (GIXRD) and Transmission electron microscopy (TEM). Identification of binding energy and concentration (x) in these films is carried out by X-ray photoelectron spectroscopy (XPS). Local crystal structure around the Cr and Ti atom of these films are investigated by X-ray absorption spectroscopy (XAS). It is found that Cr and Ti replace the Al atom in AlN lattice and the bond lengths in first and second coordination sphere with N and Al, respectively, decrease concerning doping concentration due to strong p-d hybridization. The nano-indentation hardness of Cr and Ti-doped AlN films seems to increase from 17.5 GPa (AlN) to around 23 and 27.5 GPa, respectively. An-isotropic optical properties of these films are studied by the Spectroscopic Ellipsometry technique. Refractive index and extinction coefficient of these films are enhanced in normal dispersion region as compared to the parent AlN film. The optical band gap energies also seem to vary between deep UV to UV regions with the addition of Cr, thus by bringing out the usefulness of these films in the area of optoelectronic device applications.

Keywords: ellipsometry, GIXRD, hardness, XAS

Procedia PDF Downloads 105

Authors: Stephen O. Amiandamhen, Martina Meinken, Luvuyo Tyhoda

Abstract:

The properties of Hemp (Cannabis sativa) in phosphate bonded composites were investigated in this research. Hemp hurds were collected from the Hemporium institute for research, South Africa. The hurds were air-dried and shredded using a hammer mill. The shives were screened into different particle sizes and were treated separately with 5% solution of acetic anhydride and sodium hydroxide. The binding matrix was prepared using a reactive magnesia, phosphoric acid, class S fly ash and unslaked lime. The treated and untreated hemp fibers were mixed thoroughly in different ratios with the inorganic matrix. Boric acid and excess water were used to retard and control the rate of the reaction and the setting of the binder. The Hemp composite was formed in a rectangular mold and compressed at room temperature at a pressure of 100KPa. After de-molding the composites, they were cured in a conditioning room for 96 h. Physical and mechanical tests were conducted to evaluate the properties of the composites. A central composite design (CCD) was used to determine the best conditions to optimize the performance of the composites. Thereafter, these combinations were applied in the production of the composites, and the properties were evaluated. Scanning electron microscopy (SEM) was used to carry out the advance examination of the behavior of the composites while X-ray diffractometry (XRD) was used to analyze the reaction pathway in the composites. The results revealed that all properties of phosphate bonded Hemp composites exceeded the LD-1 grade classification of particle boards. The proposed product can be used for ceiling, partitioning, wall claddings and underlayment.

Keywords: CCD, fly ash, magnesia, phosphate bonded hemp composites, phosphoric acid, unslaked lime

Procedia PDF Downloads 428

Authors: Latife Merve Oktay, Berrin Tugrul

Abstract:

Hydroxytyrosol (HT) is a phenolic phytochemical molecule derived from the hydrolysis of oleuropein, which originates during the maturation of the olives. It has recently received particular attention because of its antioxidant, anti-proliferative, pro-apoptotic and anti-inflammatory activities. In this study, we investigated the cytotoxic and apoptotic effects of hydroxytyrosol and its effects on phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and extracellular signal-regulated kinase 1/2 (ERK 1/2) signaling pathways in human ovarian cancer cell lines OVCAR-3 and MDAH-2774. XTT cell proliferation kit, Cell Death Detection Elisa Plus Kit (Roche) and Human Apoptosis Array (R&D Systems) were used to determine the cytotoxic and apoptotic effects of HT in OVCAR-3 and MDAH-2774 cell lines at 24, 48, 72, and 96 h. Effect of HT on PI3K/Akt and ERK 1/2 signaling pathways were investigated by using specific inhibitors of these pathways. IC50 values of HT were found to be 102.3 µM in MDAH-2774 cells at 72 h and 51.5 µM in OVCAR-3 cells at 96 h. Apoptotic effect of HT in MDAH-2774 cells was the highest at 50 µM at 72 h, and kept decreasing at 100 and 150 µM concentrations and was not seen at 200 µM and higher concentrations. Highest apoptotic effect was seen at 100 µM concentration in OVCAR-3 cells at 96 h, however apoptotic effect was decreased over 100 µM concentrations. According to antibody microarray results, HT increased the levels of pro-apoptotic molecules Bad, Bax, active caspase-3, Htra2/Omi by 2.0-, 1.4-, 1.2-, 4.2-fold, respectively and also increased the levels of pro-apoptotic death receptors TRAIL R1/DR4, TRAIL R2/DR5, FAS/TNFRSF6 by 2.1-, 1.7-, 1.6-fold, respectively, however, it decreased the level of Survivin by 1.6-fold which is one of the inhibitor of apoptosis protein (IAP) family in MDAH-2774 cells. In OVCAR-3 cells, HT decreased the levels of anti-apoptotic proteins Bcl-2, pro-caspase 3 by 3.1-, 8.2-fold, respectively and IAP family proteins CIAP-1, CIAP-2, XIAP, Livin, Survivin by 6.5-, 6.0-, 3.2-, 2.2-, 2.7-fold, respectively and increased the level of cytochrome-c by 1.2-fold. We have shown that HT shows its cytotoxic and apoptotic effect through inhibiting ERK 1/2 signaling pathway in both OVCAR-3 and MDAH-2774 cells. Further studies are needed to investigate molecular mechanisms and modulatory effects of hydroxytyrosol.

Keywords: apoptosis, cytotoxicity, hydroxytyrosol, ovarian cancer

Procedia PDF Downloads 347