Search results for: in-vitro drug release

Authors: Elham Rezaee, Sayyed Abbas Tabatabai

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Dual inhibition of COX-2 and sEH enzymes represents one of the distinct pharmaceutical approaches for the treatment of inflammation, pain, cancers, and other diseases. The discovery of these inhibitors for treatment is a great deal of attention because of some advantages such as increased efficacy, a promising safety profile, ease of formulation, and better target engagement. In this research, based on the structure-activity relationship of COX-2 and sEH inhibitors, some amide derivatives with oxadiazole and dihydropyrimidinone rings against sEH and COX-2 enzymes were developed. The designed compounds showed high affinity to the active site of both enzymes in docking studies and were synthesized in good yield and characterized by IR, Mass, 1HNMR, and 13CNMR. All of the novel compounds exhibited considerable in-vitro sEH and COX-2 inhibitory activities in comparison with 12-(3-Adamantan-1-yl-ureido)- dodecanoic acid and celecoxib (a potent urea-based sEH inhibitor and selective nonsteroidal anti-inflammatory drug, respectively). Ethyl 6-methyl-4-(4-(4-(methylsulfonyl)benzamido)phenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate was found to be the most selective COX-2 inhibitor (COX-2/COX-1 ratio: 683) with IC50 value of 2.1 nM targeting sEH enzyme.

Keywords: COX-2, dual inhibitors, sEH, synthesis

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Authors: Saha Saradindu, Das Payel, Somdeb BoseDasgupta

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Tuberculosis caused by Mycobacteria tuberculosis is a dreadful disease and more so with the advent of extreme and total drug-resistant species. Mycobacterial pathogenesis is an ever-changing paradigm from phagosome maturation block to phagosomal escape into macrophage cytosol and finally acid tolerance and survival inside the lysosome. Mycobacteria are adept at subverting the host immune response by highjacking host cell signaling and secreting virulence factors. One such virulence factor is a ser/thr kinase; Protein kinase G (PknG), which is known to prevent phagosome maturation. The host substrates of PknG, allowing successful pathogenesis still remain an enigma. Hence we carried out a comparative phosphoproteomic screen and identified a number of substrates phosphorylated by PknG. We characterized some of these substrates in vivo and in vitro and observed that PknG mediated phosphorylation of these substrates leads to reduced TNFa production as well as decreased response to TNFa induced macrophage necroptosis, thus enabling mycobacterial survival and proliferation.

Keywords: mycobacteria, Protein kinase G, phosphoproteomics, necroptosis

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Authors: Mahnoosh Aliahmadi, Akbar Esmaeili

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This study synthesized new modified imaging nanocapsules (NCs) of gallium@deferoxamine/folic acid/chitosan/polyaniline/polyvinyl alcohol (Ga@DFA/FA/CS/PANI/PVA) containing Morus nigra extract by selenium nanoparticles prepared from Lactobacillus acidophilus. Se nanoparticles were then deposited on (Ga@DFA/FA/CS/PANI/PVA) using the impregnation method. The modified contrast agents were mixed with M. nigra extract, and their antibacterial activities were investigated by applying them to L929 cell lines. The influence of variable factors including surfactant, solvent, aqueous phase, pH, buffer, minimum Inhibitory concentration (MIC), minimum bactericidal concentration (MBC), cytotoxicity on cancer cells, antibiotic, antibiogram, release and loading, stirring effect, the concentration of nanoparticle, olive oil, and thermotical methods was investigated. The structure and morphology of the synthesized contrast agents were characterized by zeta potential sizer analysis (ZPS), X-Ray diffraction (XRD), Fourier-transform infrared (FT-IR), and energy-dispersive X-ray (EDX), ultraviolet-visible (UV-Vis) spectra, and scanning electron microscope (SEM). The experimental section was conducted and monitored by response surface methods (RSM) and MTT conversion assay. Antibiogram testing of NCs on Pseudomonas aeruginosa bacteria was successful, and the MIC=2 factor was obtained with a less harmful effect.

Keywords: imaging contrast agent, nanoparticles, response surface method, Lactobacillus acidophilus, selenium

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Authors: Reza Hosseinpourpia, Stergios Adamopoulos, Carsten Mai

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Medium density fiberboard (MDF) is a common category of wood-based panels that are widely used in the furniture industry. Fine lignocellulosic fibres are combined with a synthetic resin, mostly urea formaldehyde (UF), and joined together under heat and pressure to form panels. Like solid wood, MDF is a hygroscopic material; therefore, its moisture content depends on the surrounding relative humidity and temperature. In addition, UF is a hydrophilic resin and susceptible to hydrolysis under certain conditions of elevated temperatures and humidity, which cause dimensional instability of the panels. The latter directly affect the performance of final products such as furniture, when they are used in situations of high relative humidity. Existing water-repellent formulations, such as paraffin, present limitations related to their non-renewable nature, cost and highest allowed added amount. Therefore, the aim of the present study was to test the suitability of renewable water repellents as alternative chemicals for enhancing the dimensional stability of MDF panels. A small amount of tall oil based formulations were used as water-repellent agents in the manufacturing of laboratory scale MDF. The effects on dimensional stability, internal bond strength and formaldehyde release of MDF were tested. The results indicated a good potential of tall oil as a bio-based substance of water repellent formulations for improving the dimensional stability of MDF.

Keywords: dimensional stability, medium density fiberboard, tall oil, urea formaldehyde

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Authors: Kina Kim

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Background: There are two types of interferon-gamma release assays (IGRAs) in use for the detection of latent tuberculosis infection (LTBI), QuantiFERON-TB Gold In-tube (QFT-GIT) and T-SPOT.TB. There are some reports that IGRA results are affected by the patient's age. This study aims to compare the results of both IGRA tests according to age groups. Methods: We reviewed 54,882 samples referred to an independent reference laboratory (Seegene Medical Foundation, Seoul, Korea) for the diagnosis of LTBI from January 1, 2021, to December 31, 2021. This retrospective study enrolled 955 patients tested using QFT-GIT and 53,927 patients tested using T-SPOT.TB. The results of both IGRAs were divided in three age groups (0-9, 10-17, and ≥18-year old). The positive rates and the indeterminate rates between QFT-GIT and T-SPOT.TB were compared. We also evaluated the differences in positive and indeterminate rates by age-group. Results: The positive rate of QFT-GIT was 20.1% (192/955) and that of T-SPOT.TB was 8.7% (4704/53927) in overall patients. The positive rates of QFT-GIT in individuals aged 0-9, 10-17, and over 18-year old were 15.4%, 13.3%, and 22.0%, respectively. The positive rates of T-SPOT.TB were 8.9%, 2.0% and 8.8%,in each agegroup, respectively.The overall prevalence of indeterminate results was 2.1% (20/955) of QFT-GIT and 0.5% (270/53927) of T-SPOT.TB. The indeterminate rates of QFT-GIT in individuals aged 0-9, 10-17, and over 18 years were 0.4%, 6.7%, and 2.6%, respectively. The indeterminate rate of T-SPOT.TB were 0.5%, 0.7% and 0.5%,in each age group, respectively. Conclusion: Our findings suggest that T-SPOT.TB has a lower rate of positive results in overall patients and a lower rate of indeterminate results than those of QFT-GIT. The highest positive rate was found in the over 18 years group for QFT-GIT, but the positive rates of T-SPOT.TB was not significantly different among groups by age. QFT-GIT showed variable and higher indeterminate rates according to age group, but T-SPOT.TB showed lower rates in all age groups(<1%).

Keywords: LTBI, IGRA, QFT-GIT, T-SPOT. TB

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Authors: Faisal A. Salih, V. V. Egorov

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Verapamil is a drug used in medicine for arrhythmia, angina, and hypertension as a calcium channel blocker. In this study, a Verapamil-selective electrode was prepared, and the concentrations of the components in the membrane were as follows: PVC (32.8 wt %), O-NPhOE (66.6 wt %), and KTPClPB (0.6 wt % or approximately 0.01 M). The inner solution containing verapamil hydrochloride 1 x 10⁻³ M was introduced, and the electrodes were conditioned overnight in 1 x 10⁻³ M verapamil hydrochloride solution in 1 x 10⁻³ M orthophosphoric acid. These studies have demonstrated that O-NPhOE and KTPClPB are the best plasticizers and ion exchangers, while both direct potentiometry and potentiometric titration methods can be used for the determination of verapamil hydrochloride in tablets and injection solutions. Normalized weights of verapamil per tablet (80.4±0.2, 80.7±0.2, 81.0±0.4 mg) were determined by direct potentiometry and potentiometric titration, respectively. Weights of verapamil per average tablet weight determined by the methods of direct potentiometry and potentiometric titration were" 80.4±0.2, 80.7±0.2 mg determined for the same set of tablets, respectively. The masses of verapamil in solutions for injection, determined by direct potentiometry for two ampoules from one set, were (5.00±0.015, 5.004±0.006) mg. In all cases, good reproducibility and excellent correspondence with the declared quantities were observed.

Keywords: verapamil, potentiometry, ion-selective electrode, lipophilic physiologically active amines

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Authors: Alisha Gupta

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Osteoarthritis (OA) is the most common form of arthritis which is a degenerative joint disease causing joints to begin to break down and underlying bones to change. This “wear and tear” most frequently affects hands, hips, and knees. This is important because OA pain is considered to be a leading cause of mobility impairment in older adults, with hip and knee OA ranked 11th highest contributors to global disability. Bone tissue engineering utilizing polymer scaffolds and hydrogels is an emerging field for treating osteoarthritis. Polymer scaffolds provide a three-dimensional structure for tissue growth, and hydrogels can be used to deliver drugs and growth factors. The combination of the two materials creates a hybrid structure that can better withstand physiological and mechanical demands while also providing a more controlled environment for drug and nutrient delivery. I think using bone tissue engineering for making scaffold-hydrogel composites that are self-regenerating and vascularizing might be useful in solving this problem. Successful implementation can reconstruct healthy, simulated bone tissue on deficient applicants.

Keywords: tissue engineering, regenerative medicine, scaffold-hydrogel composites, osteoarthritis

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Authors: Wei-Ting Kuo, Feng-Huei Lin

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Epidermal growth factor receptor (EGFR) is often constitutively stimulated in cancer owing to the binding of ligands such as epidermal growth factor (EGF), so it is necessary to investigate the interaction between EGFR and its targeting biomolecules which were over ligands binding. This study would focus on the binding affinity and adhesion force of two targeting products anti-EGFR monoclonal antibody (mAb) and peptide A to EGFR comparing with EGF. Surface plasmon resonance (SPR) was used to obtain the equilibrium dissociation constant to evaluate the binding affinity. Atomic force microscopy (AFM) was performed to detect adhesion force. The result showed that binding affinity of mAb to EGFR was higher than that of EGF to EGFR, and peptide A to EGFR was lowest. The adhesion force between EGFR and mAb that was higher than EGF and peptide A to EGFR was lowest. From the studies, we could conclude that mAb had better adhesion force and binding affinity to EGFR than that of EGF and peptide A. SPR and AFM could confirm the interaction between receptor and targeting ligand easily and carefully. It provide a platform to screen ligands for receptor targeting and drug delivery.

Keywords: adhesion force, binding affinity, epidermal growth factor receptor, target molecule

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Authors: Sarra Boughaba

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α-aminophosphonates have found a wide range of applications in organic and medicinal chemistry; they are considered as pharmacological agents, anti-inflammatory antitumor agents, and antibiotics. A number of procedures have been developed for their synthesis. However, many of these methods suffer from some disadvantages such as long reaction times, environmental pollution, utilization of organic solvents, and expensive catalysts. In the past few years, heteropolyacids have received great attention as environmentally benign catalysts for organic synthetic processes, they possess unique physicochemical properties, such as super-acidity, high thermal and chemical stability, ability to accept and release electrons and high proton mobility, and the possibility of varying their acidity and oxidizing potential. In this context, an efficient and eco-friendly protocol has been described for the synthesis of α-aminophosphonates via one pot, three component reaction catalyzed by H₆P₂W₁₈O₆₂.14H₂O as reusable catalyst, by condensation of amino acids esters, various aromatic aldehydes and triethylphosphite under solvent-free conditions, the corresponding α-aminophosphonates were formed in good yields as racemic or diastereomericmixture. All the new products were systematically characterized by IR, MS, and ¹H, ¹³C-³¹P-NMR analyses. This method offers advantages such as simplicity workup with the green aspects by avoiding expensive catalysts and toxic solvents, good yields, short reaction times.

Keywords: amino acids esters, α-aminophosphonates, H₆P₂W₁₈O₆₂.14H₂O catalyst, green chemistry

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Authors: Essia Sebai, Amel Abidi, Hayet benyeddem, Akkari Hafidh

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Herbal extracts are of particular interest to the drug industry; essential oil with significant anthelmintic activity has the potential to be used as an alternative to conventional chemical drugs. In the present study, we describe the chemical profile of Laurus nobilis essential oil (EO), the in vitro anthelmintic activity of laurel oil against Haemonchus contortus and its in vivo anthelmintic effect against the murine helminth parasite model Heligmosomoides polygyrus. The chromatographic profile of L. nobilis (EO) extracted from the leaves of L. nobilis has shown the presence of monoterpenes 1,8-cineol (Eucalyptol) (29.47%), D-Limonène (18.51%) and Linalool (10.84%) in high fractions. The in vitro anthelmintic potential was expressed by an ovicidal effect against H. contortus egg hatching with an inhibition value of 3.23 mg/mL and 87.5% of immobility of adult worms after 8 hours of exposure to 8 mg/mL of L. nobilis EO. Regarding the in vivo anthelmintic potential, L. nobilis (EO) at 2400 mg/kg completely eliminated the egg output of H. polygyrus after seven days of oral treatment, together with a 79.2% of reduction in total worm counts. Based on the obtained funding, L. nobilis EO showed promising in vitro and in vivo anthelmintic capacities against gastrointestinal parasites.

Keywords: lauris nobilis, anthelmintic, haemonchus, pylogyrus

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Authors: Fadilah Aleanizy

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Colicins are a family of bacterial toxins that kill Escherichia coli and other closely related species. The mode of action of colicins involves binding to an outer membrane receptor and translocation across the cell envelope, leading to cytotoxicity through specific targets. The mechanism of colicin cytotoxicity includes a non-specific endonuclease activity or depolarization of the cytoplasmic membrane by pore-forming activity. For Group A colicins, translocation requires an interaction between the N-terminal domain of the colicin and a series of membrane- bound and periplasmic proteins known as the Tol system (TolB, TolR, TolA, TolQ, and Pal and the active domain must be translocated through the outer membranes. Protein-protein interactions are intrinsic to virtually every cellular process. The transient protein-protein interactions of the colicin include the interaction with much more complicated assemblies during colicin translocation across the cellular membrane to its target. The potassium release assay detects variation in the K+ content of bacterial cells (K+in). This assays is used to measure the effect of pore-forming colicins such as ColA on an indicator organism by measuring the changes of the K+ concentration in the external medium (K+out ) that are caused by cell killing with a K+ selective electrode. One of the goals of this work is to employ a quantifiable in-vivo method to spot which Tol protein are more implicated in the interaction with colicin A as it is translocated to its target.

Keywords: K+ efflux, Colicin A, Tol-proteins, E. coli

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Authors: Suzanne Overstreet-Juenke

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Disproportionate minority contact (DMC) is a salient issue that has been found at every stage of the decision-making process in the juvenile justice system. Existing research indicates that DMC influences adjudication for drug, property, and personal crimes. Because intimate partner violence (IPV) is a major public health problem and global concern, the current study examines DMC at adjudication among youth charged for crimes of interpersonal violence. This research uses administrative, Court Designated Worker (CDW) data collected from 2014 to 2016. The results are contextualized using Steffensmeier’s version of focal concerns theory of judicial decision-making. This study assesses race and two seriousness of offense measures to establish whether a link exists between race and adjudication. The results of the study is similar to prior research on the topic. These results are discussed in terms of policy implications, limitations, and future research.

Keywords: race, disproportionate minority contact, focal concerns theory, juvenile

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Authors: M. Hussaina, K. Mahboobb, S. Z. Ilyasa, S. Shaheena

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Plume dispersion modeling is a computational procedure to establish a relationship between emissions, meteorology, atmospheric concentrations, deposition and other factors. The emission characteristics (stack height, stack diameter, release velocity, heat contents, chemical and physical properties of the gases/particle released etc.), terrain (surface roughness, local topography, nearby buildings) and meteorology (wind speed, stability, mixing height, etc.) are required for the modeling of the plume dispersion and estimation of ground and air concentration. During the early phase of Fukushima accident, plume dispersion modeling and decisions were taken for the implementation of protective measures. A difference in estimated results and decisions made by different countries for taking protective actions created a concern in local and international community regarding the exact identification of the safe zone. The current study is focused to highlight the importance of accurate and exact weather data availability, scientific approach for decision making for taking urgent protective actions, compatible and harmonized approach for plume dispersion modeling during a nuclear emergency. As a case study, the influence of meteorological data on plume dispersion modeling and decision-making process has been performed.

Keywords: decision making process, radiation doses, nuclear emergency, meteorological implications

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Authors: Atul Srivastava, D. V. Gowda

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Enterotoxigenic Escherichia coli (ETEC) infection is one of the major causes contributing to the development of diarrhoea in adults and children in developing countries. To date, no preventive/treatment strategy showed promising results, which could be due to the lack of potent vaccines, and/or due to the development of resistance of ETEC to antibiotics. Therefore, in the present investigation, a novel porous Sodium Alginate (SA) tablet formulation loaded with F4 fimbriae antigen was developed and tested for efficacy against ETEC infections in piglet models. Pre-compression parameters of the powder mixes and post compression parameters of tablets have been evaluated and results were found to be satisfactory. Loading of F4 fimbrial antigens in to the tablets was achieved by inducing pores in the tablets via the sublimation of camphor followed by incubation with purified F4 fimbriae. The loaded tablets have been coated with Eudragit L100 to protect the F4 fimbriae from (a) highly acidic gastric environment; (b) proteolytic cleavage by pepsin; and (c) to promote subsequent release in the intestine. Evaluation of developed F4 fimbrial tablets in a Pig model demonstrated induction of mucosal immunity, and a significant reduction of F4+ E. coli in faeces. Therefore, F4 fimbriae loaded porous tablets could be a novel oral vaccination candidate to induce mucosal and systemic immunity against ETEC infections.

Keywords: porous tablets, sublimation, f4 fimbriae, eudragit l100, vaccination

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Authors: S. K. Hemalata, M. N. Shiva Kameshwari

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The present work focusses on anti-inflammatory action of Urginea wightii in-vitro. Urginea wightii is a member of Hyacinthaceae and considered to be wonder plant because of its varied important medicinal properties. The plant is endemic to India, Africa, and Mediterranian regions. Presence of alkaloids, flavonoid-glycosides especially flavonone derivatives are responsible for the strong anti-inflammatory activity of Urginea wightii. In present research work, anti-inflammatory activity of methanol extract of the bulb powder was tested on Male Wistar Rats. In these test animals, inflammation was induced by injecting carrageenan as the irritant to induce paw edema in Wistar rats. Inflammation of Paw edema was treated with both plant extract and Pyrox gel a known synthetic anti-inflammatory drug through external application. The result indicated that anti-inflammatory activity of Urginea wightii extract was almost similar to the synthetic Pyrox gel. This disproves the modern world's scepticism towards the herbal medicines and encourages to rely on natural plant extracts.

Keywords: anti-inflammatory activity, flavonoid-glycosides, Pyrox gel, Urginia wightii

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Authors: L. Malic, X. Zhang, D. Brassard, L. Clime, J. Daoud, C. Luebbert, V. Barrere, A. Boutin, S. Bidawid, N. Corneau, J. Farber, T. Veres

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The incidence of infections caused by foodborne pathogens such as Listeria monocytogenes (L. monocytogenes) poses a great potential threat to public health and safety. These issues are further exacerbated by legal repercussions due to “zero tolerance” food safety standards adopted in developed countries. Unfortunately, a large number of related disease outbreaks are caused by pathogens present in extremely low counts currently undetectable by available techniques. The development of highly sensitive and rapid detection of foodborne pathogens is therefore crucial, and requires robust and efficient pre-analytical sample preparation. Immunomagnetic separation is a popular approach to sample preparation. Microfluidic chips combined with external magnets have emerged as viable high throughput methods. However, external magnets alone are not suitable for the capture of nanoparticles, as very strong magnetic fields are required. Devices that incorporate externally applied magnetic field and microstructures of a soft magnetic material have thus been used for local field amplification. Unfortunately, very complex and costly fabrication processes used for integration of soft magnetic materials in the reported proof-of-concept devices would prohibit their use as disposable tools for food and water safety or diagnostic applications. We present a sample preparation magnetic microfluidic device implemented in low-cost thermoplastic polymers using fabrication techniques suitable for mass-production. The developed magnetic capture chip (M-chip) was employed for rapid capture and release of L. monocytogenes conjugated to immunomagnetic nanoparticles (IMNs) in buffer and beef filtrate. The M-chip relies on a dense array of Nickel-coated high-aspect ratio pillars for capture with controlled magnetic field distribution and a microfluidic channel network for sample delivery, waste, wash and recovery. The developed Nickel-coating process and passivation allows generation of switchable local perturbations within the uniform magnetic field generated with a pair of permanent magnets placed at the opposite edges of the chip. This leads to strong and reversible trapping force, wherein high local magnetic field gradients allow efficient capture of IMNs conjugated to L. monocytogenes flowing through the microfluidic chamber. The experimental optimization of the M-chip was performed using commercially available magnetic microparticles and fabricated silica-coated iron-oxide nanoparticles. The fabricated nanoparticles were optimized to achieve the desired magnetic moment and surface functionalization was tailored to allow efficient capture antibody immobilization. The integration, validation and further optimization of the capture and release protocol is demonstrated using both, dead and live L. monocytogenes through fluorescence microscopy and plate- culture method. The capture efficiency of the chip was found to vary as function of listeria to nanoparticle concentration ratio. The maximum capture efficiency of 30% was obtained and the 24-hour plate-culture method allowed the detection of initial sample concentration of only 16 cfu/ml. The device was also very efficient in concentrating the sample from a 10 ml initial volume. Specifically, 280% concentration efficiency was achieved in 17 minutes only, demonstrating the suitability of the system for food safety applications. In addition, flexible design and low-cost fabrication process will allow rapid sample preparation for applications beyond food and water safety, including point-of-care diagnosis.

Keywords: array of pillars, bacteria isolation, immunomagnetic sample preparation, polymer microfluidic device

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Authors: D. Benmoussa, H. Hannache, O. Cherkaoui

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In textiles, the major interest in microencapsulation is currently in the application of durable fragrances, skin softeners, phase-change materials, antimicrobial agents and drug delivery systems onto textile materials. In our research “Polyethylene Glycol” was applied as phase change material and it was encapsulated in polymethacrylic acid (PMA) by radical polymerization in suspension of methacrylic acid in presence of N,N'-methylenebisacrylamide (MBAM) as crosslinking agent. Thereafter the obtained microcapsule was modified by amidation with ethylenediamine as a spacer molecule. At the end of this spacer trichlorotriazine reactive group was fixed. Microcapsules were grafted onto cotton textile substrate. The surface morphologies of the microencapsulated phase change materials (micro PCMs) were studied by scanning electron microscopy (SEM). Thermal properties, thermal reliabilities and thermal stabilities of the as-prepared micro PCMs were investigated by differential scanning calorimetry (DSC) and thermogravmetric analysis (TGA). The results obtained show the obtaining microcapsules with a mean diameter of 10 µm and the resistance of the microcapsules is demonstrated by thermal analysis.

Keywords: energy storage, microencapsulation, phase-change materials, thermogravmetric analysis (TGA)

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Authors: Michaela Chovancova, Pavel Niedoba

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For the treatment of acute and chronic lung diseases it is preferred to deliver medicaments by inhalation. The drug is delivered directly to tracheobronchial tree. This way allows the given medicament to get directly into the place of action and it makes rapid onset of action and maximum efficiency. The transport of aerosol particles in the particular part of the lung is influenced by their size, anatomy of the lungs, breathing pattern and airway resistance. This article deals with calculation of airway resistance in the lung model of Horsfield. It solves the problem of determination of the pressure losses in bifurcation and thus defines the pressure drop at a given location in the bronchial tree. The obtained data will be used as boundary conditions for transport of aerosol particles in a central part of bronchial tree realized by Computational Fluid Dynamics (CFD) approach. The results obtained from CFD simulation will allow us to provide information on the required particle size and optimal inhalation technique for particle transport into particular part of the lung.

Keywords: human lungs, bronchial tree, pressure losses, airways resistance, flow, breathing

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Authors: Rahul Agarwal, Ashutosh Singh

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Colorectal cancer (CRC) also refers as bowel cancer or colon cancer. It involves the development of abnormal growth of cells in colon or rectum part of the body. This work leads to the development of a miRNA database in colorectal cancer. We named this database- miCoRe. This database comprises of all validated colon-rectal cancer miRNAs information from various published literature with an effectual knowledge based information retrieval system. miRNAs have been collected from various published literature reports. MySQL is used for main-framework of miCoRe while the front-end was developed in PHP script. The aim of developing miCoRe is to create a comprehensive central repository of colorectal carcinoma miRNAs with all germane information of miRNAs and their target genes. The current version of miCoRe consists of 238 miRNAs which are known to be implicated in malignancy of CRC. Alongside with miRNA information, miCoRe also contains the information related to the target genes of these miRNA. miCoRe furnishes the information about the mechanism of incidence and progression of the disease, which would further help the researchers to look for colorectal specific miRNAs therapies and CRC specific targeted drug designing. Moreover, it will also help in development of biomarkers for the better and early detection of CRC and will help in better clinical management of the disease.

Keywords: colorectal cancer, database, miCoRe, miRNAs

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Authors: J. Ticona Chambi, E. A. De Almeida, C. A. Andrade Raymundo Gaiotto, A. M. Do Espírito Santo, L. Infantes, S. L. Cuffini

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The solubility of active pharmaceutical ingredients (APIs) is challenging for the pharmaceutical industry. The new multicomponent crystalline forms as cocrystal and solvates present an opportunity to improve the solubility of APIs. Commonly, the procedure to obtain multicomponent crystalline forms of a drug starts by screening the drug molecule with the different coformers/solvents. However, it is necessary to develop methods to obtain multicomponent forms in an efficient way and with the least possible environmental impact. The Hansen Solubility Parameters (HSPs) is considered a tool to obtain theoretical knowledge of the solubility of the target compound in the chosen solvent. H-Bond Propensity (HBP), Molecular Complementarity (MC), Coordination Values (CV) are tools used for statistical prediction of cocrystals developed by the Cambridge Crystallographic Data Center (CCDC). The HSPs and the CCDC tools are based on inter- and intra-molecular interactions. The curcumin (Cur), target molecule, is commonly used as an anti‐inflammatory. The demethoxycurcumin (Demcur) and bisdemethoxycurcumin (Bisdcur) are natural analogues of Cur from turmeric. Those target molecules have differences in their solubilities. In this way, the work aimed to analyze and compare different tools for multicomponent forms prediction (solvates) of Cur, Demcur and Biscur. The HSP values were calculated for Cur, Demcur, and Biscur using the chemical group contribution methods and the statistical optimization from experimental data. The HSPmol software was used. From the HSPs of the target molecules and fifty solvents (listed in the HSP books), the relative energy difference (RED) was determined. The probability of the target molecules would be interacting with the solvent molecule was determined using the CCDC tools. A dataset of fifty molecules of different organic solvents was ranked for each prediction method and by a consensus ranking of different combinations: HSP, CV, HBP and MC values. Based on the prediction, 15 solvents were selected as Dimethyl Sulfoxide (DMSO), Tetrahydrofuran (THF), Acetonitrile (ACN), 1,4-Dioxane (DOX) and others. In a starting analysis, the slow evaporation technique from 50°C at room temperature and 4°C was used to obtain solvates. The single crystals were collected by using a Bruker D8 Venture diffractometer, detector Photon100. The data processing and crystal structure determination were performed using APEX3 and Olex2-1.5 software. According to the results, the HSPs (theoretical and optimized) and the Hansen solubility sphere for Cur, Demcur and Biscur were obtained. With respect to prediction analyses, a way to evaluate the predicting method was through the ranking and the consensus ranking position of solvates already reported in the literature. It was observed that the combination of HSP-CV obtained the best results when compared to the other methods. Furthermore, as a result of solvent selected, six new solvates, Cur-DOX, Cur-DMSO, Bicur-DOX, Bircur-THF, Demcur-DOX, Demcur-ACN and a new Biscur hydrate, were obtained. Crystal structures were determined for Cur-DOX, Biscur-DOX, Demcur-DOX and Bicur-Water. Moreover, the unit-cell parameter information for Cur-DMSO, Biscur-THF and Demcur-ACN were obtained. The preliminary results showed that the prediction method is showing a promising strategy to evaluate the possibility of forming multicomponent. It is currently working on obtaining multicomponent single crystals.

Keywords: curcumin, HSPs, prediction, solvates, solubility

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Authors: Naveen Kumar

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Microplastics, tiny plastic particles less than 5 mm in size formed by the disposal and breakdown of industrial and consumer products, have become a primary environmental concern due to their ubiquitous presence and application in the environment and their potential to cause harm to the ecosystem, wildlife and human health. In this, we study the ability of the fungus Rasamsonia emersonii IMI 393752 to degrade the rigid microplastics of Coke bottles. Microplastics were extracted from Coke bottles and incubated with Rasamsonia emersonii in Sabouraud dextrose agar media. Microplastics were pre-sterilized without altering the chemistry of microplastic. Preliminary analysis was performed by observing radial growth assessment of microplastic-containing media enriched with fungi vs. control. The assay confirmed no impedance or change in the fungi's growth pattern and rate by introducing microplastics. The degradation of the microplastics was monitored over time using microscopy and FTIR, and biodegradation/deterioration on the plastic surface was observed. Furthermore, the liquid assay was performed. HPLC and GCMS will be conducted to check the biodegradation and presence of enzyme release by fungi to counteract the presence of microplastics. These findings have important implications for managing plastic waste, as they suggest that fungi such as Rasamsonia emersonii can potentially degrade microplastics safely and effectively. However, further research to optimise the conditions for microplastic degradation by Rasamsonia emersonii and to develop strategies for scaling up the process for industrial applications will be beneficial.

Keywords: bioremediation, mycoremediation, plastic degradtion, polyethylene terephthalate

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Authors: Pablo Reche

Abstract:

Since 1980’s aquaculture has become the biggest economic activity in southern Chile, being Salmo salar and Oncorhynchus mykiss the main finfish species. High fish density makes both species prone to contract diseases, what drives the industry to big losses, affecting greatly the local economy. Three are the most concerning infective agents, the infectious salmon anemia virus (ISAv), the bacteria Piscirickettsia salmonis and the copepod Caligus rogercresseyi. To regulate the industry the government arranged the salmon farms within management areas named as barrios, which coordinate the fallowing periods and antibiotics treatments of their salmon farms. In turn, barrios are gathered into larger management areas, named as macrozonas whose purpose is to minimize the risk of disease transmission between them and to enclose the outbreaks within their boundaries. However, disease outbreaks still happen and transmission to neighbor sites enlarges the initial event. Salmon disease agents are mostly transported passively by local currents. Thus, to understand how transmission occurs it must be firstly studied the physical environment. In Chile, salmon farming takes place in the inner seas of the southernmost regions of western Patagonia, between 41.5ºS-55ºS. This coastal marine system is characterised by western winds, latitudinally modulated by the position of the South-Eats Pacific high-pressure centre, high precipitation rates and freshwater inflows from the numerous glaciers (including the largest ice cap out of Antarctic and Greenland). All of these forcings meet in a complex bathymetry and coastline system - deep fjords, shallow sills, narrow straits, channels, archipelagos, inlets, and isolated inner seas- driving an estuarine circulation (fast outflows westwards on surface and slow deeper inflows eastwards). Such a complex system is modelled on the numerical model MIKE3, upon whose 3D current fields particle-track-biological models (one for each infective agent) are decoupled. Each agent biology is parameterized by functions for maturation and mortality (reproduction not included). Such parameterizations are depending upon environmental factors, like temperature and salinity, so their lifespan will depend upon the environmental conditions those virtual agents encounter on their way while passively transported. CLIC (Connectivity-Langrangian–IFOP-Chile) is a service platform that supports the graphical visualization of the connectivity matrices calculated from the particle trajectories files resultant of the particle-track-biological models. On CLIC users can select, from a high-resolution grid (~1km), the areas the connectivity will be calculated between them. These areas can be barrios and macrozonas. Users also can select what nodes of these areas are allowed to release and scatter particles from, depth and frequency of the initial particle release, climatic scenario (winter/summer) and type of particle (ISAv, Piscirickettsia salmonis, Caligus rogercresseyi plus an option for lifeless particles). Results include probabilities downstream (where the particles go) and upstream (where the particles come from), particle age and vertical distribution, all of them aiming to understand how currently connectivity works to eventually propose a minimum risk zonation for aquaculture purpose. Preliminary results in Chiloe inner sea shows that the risk depends not only upon dynamic conditions but upon barrios location with respect to their neighbors.

Keywords: aquaculture zonation, Caligus rogercresseyi, Chilean Patagonia, coastal oceanography, connectivity, infectious salmon anemia virus, Piscirickettsia salmonis

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Authors: Joan O. Ogundele, Aladesanmi A. Oshodi, Adekunle I. Amoo

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Abstract In-vitro multi-enzyme protein digestibility (IVMPD) and some anti-nutritional factors (ANF) of five melon (egusi) seed flours (MSF) and their protein isolates (PI) were carried out. Their PI have potentials comparable to that of soya beans. It is important to know the IVMPD and ANF of these protein sources as to ensure their safety when adapted for use as alternate protein sources to substitute for cow milk, which is relatively expensive in Nigeria. Standard methods were used to produce PI of Citrullus colocynthis, Citrullus vulgaris, African Wine Kettle gourd (Lageneria siceraria I), Basket Ball gourd (Lagenaria siceraria II) and Bushel Giant Gourd (Lageneria siceraria III) seeds and to determine the ANF and IVMPD of the MSF and PI unheated and at 37oC. Multi-enzymes used were trypsin, chymotrypsin and peptidase. IVMPD of MSF ranged from (70.67±0.70) % (C. vulgaris) to (72.07± 1.79) % (L.siceraria I) while for their PI ranged from 74.33% (C.vulgaris) to 77.55% (L.siceraria III). IVMPD of the PI were higher than those of MSF. Heating increased IVMPD of MSF with average value of 79.40% and those of PI with average of 84.14%. ANF average in MSF are tannin (0.11mg/g), phytate (0.23%). Differences in IVMPD of MSF and their PI at different temperatures may arise from processing conditions that alter the release of amino acids from proteins by enzymatic processes. ANF in MSF were relatively low, but were found to be lower in the PI, therefor making the PI safer for human consumption as an alternate source of protein.

Keywords: Anti-nutrients, Enzymatic protein digestibility, Melon (egusi)., Protein Isolates.

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Authors: Nantawan Soonklang, Linda Chularojanamontri, Urarat Nanna

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Ethnopharmacological relevance: Thunbergia laurifolia Lindl. belongs to the family Acanthaceae commonly known as Rang jeud in Thailand. This plant is traditionally used in Thailand for centuries as an antidote for several poisons and drug overdose. Aim of the study: This research aimed to study the analgesic and antipyretic activities of T. laurifolia water extract by using animal models. Materials and Methods: The analgesic activity was studied using 2 methods of pain induction including acetic acid and heat induced pain. And the antipyretic activity study was performed by yeast-induced hyperthermia. Results: The results showed that the administration of T. laurifolia extract possessed analgesic activity by reducing acetic acid-induced writhing response and heat-induced pain as well as showed antipyretic activity by decreasing body temperature of hyperthermic rats induced by brewer’s yeast. Conclusion: The study indicates that the T. laurifolia extract possesses analgesic and antipyretic activities in animals.

Keywords: Thunbergia laurifolia extract, analgesic activity, antipyretic activity, hyperthermia

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Authors: A. Zonouzi, M. Auli, M. Javanmard Dakheli, M. A. Hejazi

Abstract:

Microalgae are tiny photosynthetic plants. Nowadays, microalgae are being used as nutrient-dense foods and sources of fine chemicals. They have significant amounts of lipid, carotenoids, vitamins, protein, minerals, chlorophyll, and pigments. Oil extraction from algae is a hotly debated topic currently because introducing an efficient method could decrease the process cost. This can determine the sustainability of algae-based foods. Scientific research works show that solvent extraction using chloroform/methanol (2:1) mixture is one of the efficient methods for oil extraction from algal cells, but both methanol and chloroform are toxic solvents, and therefore, the extracted oil will not be suitable for food application. In this paper, the effect of two food grade solvents (hexane and hexane/ isopropanol) on oil extraction yield from microalgae Dunaliella sp. was investigated and the results were compared with chloroform/methanol (2:1) extraction yield. It was observed that the oil extraction yield using hexane, hexane/isopropanol (3:2) and chloroform/methanol (2:1) mixture were 5.4, 13.93, and 17.5 (% w/w, dry basis), respectively. The fatty acid profile derived from GC illustrated that the palmitic (36.62%), oleic (18.62%), and stearic acids (19.08%) form the main portion of fatty acid composition of microalgae Dunalliela sp. oil. It was concluded that, the addition of isopropanol as polar solvent could increase the extraction yield significantly. Isopropanol solves cell wall phospholipids and enhances the release of intercellular lipids, which improves accessing of hexane to fatty acids.

Keywords: fatty acid profile‎, microalgae‎, oil extraction‎, polar solvent‎

Procedia PDF Downloads 379

Authors: Sangbok Lee

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There has been much effort on process improvement for outpatient clinics to provide quality and acute care to patients. One of the efforts is no-show analysis or prediction. This work analyzes patient no-shows along with patient health conditions. The health conditions refer to clinical symptoms that each patient has, out of the followings; hyperlipidemia, diabetes, metastatic solid tumor, dementia, chronic obstructive pulmonary disease, hypertension, coronary artery disease, myocardial infraction, congestive heart failure, atrial fibrillation, stroke, drug dependence abuse, schizophrenia, major depression, and pain. A dataset from a regional hospital is used to find the relationship between the number of the symptoms and no-show probabilities. Additional analysis reveals how each symptom or combination of symptoms affects no-shows. In the above analyses, cross-classification of patients by age and gender is carried out. The findings from the analysis will be used to take extra care to patients with particular health conditions. They will be forced to visit clinics by being informed about their health conditions and possible consequences more clearly. Moreover, this work will be used in the preparation of making institutional guidelines for patient reminder systems.

Keywords: healthcare system, no show analysis, process improvment, statistical data analysis

Procedia PDF Downloads 233

Authors: Raquel Dafouz Neus Cáceres, Javier Fernandez-Rubio, Belinda Huerta José Luis Rodríguez-Gil, Nicola Mastroianni, Miren López de Alda, Damià Barceló, Yolanda Valcárcel

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The region of Galicia, found in north-western (NW) Spain, is a national and world leader in shellfish, especially mussel production, and recognized for its fishing industry. Few studies have evaluated the presence of emerging contaminants in NW Spain, with those published mainly concerning the continental aquatic environment. The objective of this study was to identify the environmental risk posed by the presence of pharmaceuticals and drugs of abuse in this important coastal region. The presence of sixteen pharmaceuticals (benzodiazepines, anxiolytics, and caffeine), and 19 drugs of abuse (cocainics, amphetamine-like compounds, opiates and opioids, lysergic compounds, and cannabinoids) was assessed in 23 sites located in the Rías (Coastal inlets) of Muros, Arousa, and Pontevedra (NW Spain). Twenty-two of these locations were affected by waste-water treatment plant (WWTP) effluents, and one represented the effluent of one of these WWTPs. Venlafaxine was the pharmaceutical compound detected at higher concentration in the three Rías, with a maximum value of 291 ng/L at the site Porto do Son (Ría de Muros). Total concentration in the three Rías was 819,26 ng/L. Next, citalopram and lorazepam were the most prevalent compounds detected. Metabolite of cocaine benzoylecgonine was the drug of abuse with the highest concentration, measured at 972 ng/L in the Ría of Noia WWTP (no dilution). This compound was also detected at 142 ng/L in the site La Isla de Aros, Ría of Pontevedra. Total concentration for the three Rías was 1210 ng/L. Ephedrine was also detected at high level in the three Rías, with a total concentration of 579,28 ng/L. The results obtained for caffeine show maximum and average concentrations of 857 ng/L Isla de Arosa, Ría de Pontevedra the highest measured in seawater in Spain. A preliminary hazard assessment was carried out by comparing these measured environmental concentrations (MEC) to predicted no-effect concentrations (PNECs) for aquatic organisms. Six out of the 22 seawater samples resulted in a Hazard Quotient (HQ) from chronic exposure higher than 1 with the highest being 17.14, indicating a high probability of adverse effects in the aquatic environment. In addition, the risk was assessed on the basis of persistence, bioaccumulation, and toxicity (PBT). This work was financially supported by the Spanish Ministry of Economy and Competitiveness through the Carlos III Health Institute and the program 'Proyectos de Investigacion en Salud 2015-2017' FIS (PI14/00516), the European Regional Development Fund (ERDF), the Catalan Government (Consolidated Research Groups '2014 SGR 418 - Water and Soil Quality Unit' and 2014 SGR 291 - ICRA), and the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 603437. The poster entitled 'Environmental Risk of Pharmaceuticals, Drugs of Abuse and Stimulant Caffeine in Marine Water: A Case Study in the North-Western of Spain'.

Keywords: drug of abuse, pharmaceuticals, caffeine, environmental risk, seawater

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Authors: Siao-Wei Jiang, Boy-Young Hsieh, Ching-Liang Hsieh, Cheng-Yung Lin

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The problems of multiple drug resistance in the pig farming industry have been emphasized in recent years. Diarrhea syndrome is common in weaning piglets and often treated with antibiotics as a feed additive, leading to the rapid spread of antibiotic resistance and posing high health risks to humans. The study aimed to alleviate diarrhea syndrome with traditional herbal medicine, Xiang Sha Liu Jun Zi Tang, whose effects enhanced digestive function. Piglets at 4 weeks old with stool classified to Bristol stool classification type 6 or type 7 were randomly divided into the control group, group A (1% of Xiang Sha Liu Jun Zi Tang) and group B (0.1% Colistin). The piglets were administrated for 7 days, and their weight, feed intake, and stool score were recorded daily before and after the trial. The results showed that the diarrhea index score in group A and group B improved significantly compared to the control group, indicating that Xiang Sha Liu Jun Zi Tang may have the same effect on alleviating diarrhea syndrome as Colistin, and it may be another replacement for antibiotics.

Keywords: pig, diarrhea, herbal medicine, Xiang Sha Liu Jun Zi Tang

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Authors: Adenike Adesanya, Nonthaphat Wong, Xiang-Yun Lan, Shea Ping Yip, Chien-Ling Huang

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Background: The most challenging mutation of the oncokinase BCR-ABL protein T315I, which is commonly known as the “gatekeeper” mutation and is notorious for its strong resistance to almost all tyrosine kinase inhibitors (TKIs), especially imatinib. Therefore, this study aims to identify T315I-dependent downstream microRNA (miRNA) pathways associated with drug resistance in chronic myeloid leukemia (CML) for prognostic and therapeutic purposes. Methods: T315I-carrying K562 cell clones (K562-T315I) were generated by the CRISPR-Cas9 system. Imatinib-treated K562-T315I cells were subjected to small RNA library preparation and next-generation sequencing. Putative lncRNA-miRNA-mRNA networks were analyzed with (i) DESeq2 to extract differentially expressed miRNAs, using Padj value of 0.05 as cut-off, (ii) STarMir to obtain potential miRNA response element (MRE) binding sites of selected miRNAs on lncRNA H19, (iii) miRDB, miRTarbase, and TargetScan to predict mRNA targets of selected miRNAs, (iv) IntaRNA to obtain putative interactions between H19 and the predicted mRNAs, (v) Cytoscape to visualize putative networks, and (vi) several pathway analysis platforms – Enrichr, PANTHER and ShinyGO for pathway enrichment analysis. Moreover, mitochondria isolation and transcript quantification were adopted to determine the new mechanism involved in T315I-mediated resistance of CML treatment. Results: Verification of the CRISPR-mediated mutagenesis with digital droplet PCR detected the mutation abundance of ≥80%. Further validation showed the viability of ≥90% by cell viability assay, and intense phosphorylated CRKL protein band being detected with no observable change for BCR-ABL and c-ABL protein expressions by Western blot. As reported by several investigations into hematological malignancies, we determined a 7-fold increase of H19 expression in K562-T315I cells. After imatinib treatment, a 9-fold increment was observed. DESeq2 revealed 171 miRNAs were differentially expressed K562-T315I, 112 out of these miRNAs were identified to have MRE binding regions on H19, and 26 out of the 112 miRNAs were significantly downregulated. Adopting the seed-sequence analysis of these identified miRNAs, we obtained 167 mRNAs. 6 hub miRNAs (hsa-let-7b-5p, hsa-let-7e-5p, hsa-miR-125a-5p, hsa-miR-129-5p, and hsa-miR-372-3p) and 25 predicted genes were identified after constructing hub miRNA-target gene network. These targets demonstrated putative interactions with H19 lncRNA and were mostly enriched in pathways related to cell proliferation, senescence, gene silencing, and pluripotency of stem cells. Further experimental findings have also shown the up-regulation of mitochondrial transcript and lncRNA MALAT1 contributing to the lncRNA-miRNA-mRNA networks induced by BCR-ABL T315I mutation. Conclusions: Our results have indicated that lncRNA-miRNA regulators play a crucial role not only in leukemogenesis but also in drug resistance, considering the significant dysregulation and interactions in the K562-T315I cell model generated by CRISPR-Cas9. In silico analysis has further shown that lncRNAs H19 and MALAT1 bear several complementary miRNA sites. This implies that they could serve as a sponge, hence sequestering the activity of the target miRNAs.

Keywords: chronic myeloid leukemia, imatinib resistance, lncRNA-miRNA-mRNA, T315I mutation

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Authors: Amin Pashaye Amiri

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Freedom of information, according to which the public has a right to have access to government-held information, is largely considered as a tool for improving transparency and accountability in governments, and as a requirement of self-governance and good governance. So far, more than ninety countries have recognized citizens’ right to have access to public information. This recognition often took place through the adoption of an act referred to as “freedom of information act”, “access to public records act”, and so on. A freedom of information act typically imposes a positive obligation on a government to initially and regularly release certain public information, and also obliges it to provide individuals with information they request. Such an act usually allows governmental bodies to withhold information only when it falls within a limited number of exemptions enumerated in the act such as exemptions for protecting privacy of individuals and protecting national security. Some steps have been taken at the national and international level towards the recognition of freedom of information as a human right. Freedom of information was recognized in a few countries as a part of freedom of expression, and therefore, as a human right. Freedom of information was also recognized by some international bodies as a human right. The Inter-American Court of Human Rights ruled in 2006 that Article 13 of the American Convention on Human Rights, which concerns the human right to freedom of expression, protects the right of all people to request access to government information. The European Court of Human Rights has recently taken a considerable step towards recognizing freedom of information as a human right. However, in spite of the measures that have been taken, public access to government information is not yet widely accepted as an international human right. The paper will consider the degree to which freedom of information has been recognized as a human right, and study the possibility of widespread recognition of such a human right in the future. It will also examine the possible benefits of such recognition for the development of the human right to free expression.

Keywords: freedom of information, freedom of expression, human rights, government information

Procedia PDF Downloads 550